which biomarkers predict the severe clinical course of 2019-nCOV infection?

Clinical and biochemical indexes from 2019-nCoV infected patients linked to viral loads and lung injury

The outbreak of the 2019-nCoV infection began in December 2019 in Wuhan, Hubei province, and rapidly spread to many provinces in China as well as other countries. Here we report the epidemiological, clinical, laboratory, and radiological characteristics, as well as potential biomarkers for predicting disease severity in 2019-nCoV-infected patients in Shenzhen, China. All 12 cases of the 2019-nCoV-infected patients developed pneumonia and half of them developed acute respiratory distress syndrome (ARDS). The most common laboratory abnormalities were hypoalbuminemia, lymphopenia, decreased percentage of lymphocytes (LYM) and neutrophils (NEU), elevated C-reactive protein (CRP) and lactate dehydrogenase (LDH), and decreased CD8 count. The viral load of 2019-nCoV detected from patient respiratory tracts was positively linked to lung disease severity. ALB, LYM, LYM (%), LDH, NEU (%), and CRP were highly correlated to the acute lung injury. Age, viral load, lung injury score, and blood biochemistry indexes, albumin (ALB), CRP, LDH, LYM (%), LYM, and NEU (%), may be predictors of disease severity. Moreover, the Angiotensin II level in the plasma sample from 2019-nCoV infected patients was markedly elevated and linearly associated to viral load and lung injury. Our results suggest a number of potential diagnosis biomarkers and angiotensin receptor blocker (ARB) drugs for potential repurposing treatment of 2019-nCoV infection. ELECTRONIC SUPPLEMENTARY MATERIAL: Supplementary material is available for this article at 10.1007/s11427-020-1643-8 and is accessible for authorized users.

Single-cell Analysis of ACE2 Expression in Human Kidneys and Bladders Reveals a Potential Route of 2019-nCoV Infection

Since December 2019, a novel coronavirus named 2019 coronavirus (2019-nCoV) has emerged in Wuhan of China and spread to several countries worldwide within just one month. Apart from fever and respiratory complications, acute kidney injury has been observed in some patients with 2019-nCoV. In a short period of time, angiotensin converting enzyme II (ACE2), have been proposed to serve as the receptor for the entry of 2019-nCoV, which is the same for severe acute respiratory syndrome coronavirus (SARS). To investigate the possible cause of kidney damage in 2019-nCoV patients, we used both published kidney and bladder cell atlas data and an independent unpublished kidney single cell RNA-Seq data generated in-house to evaluate ACE2 gene expressions in all cell types in healthy kidneys and bladders. Our results showed the enriched expression of all subtypes of proximal tubule cells of kidney and low but detectable levels of expression in bladder epithelial cells. These results indicated the urinary system is a potential route for 2019-nCoV infection, along with the respiratory system and digestion system. Our findings suggested the kidney abnormalities of SARS and 2019-nCoV patients may be due to proximal tubule cells damage and subsequent systematic inflammatory response induced kidney injury. Beyond that, laboratory tests of viruses and related indicators in urine may be needed in some special patients of 2019-nCoV.

Neutrophil-to-Lymphocyte Ratio Predicts Severe Illness Patients with 2019 Novel Coronavirus in the Early Stage

Background: Severe ill patients with 2019 novel coronavirus (2019-nCoV) infection progressed rapidly to acute respiratory failure. We aimed to select the most useful prognostic factor for severe illness incidence. Methods: The study prospectively included 61 patients with 2019-nCoV infection treated at Beijing Ditan Hospital from January 13, 2020 to January 31, 2020. Prognostic factor of severe illness was selected by the LASSO COX regression analyses, to predict the severe illness probability of 2019-CoV pneumonia. The predictive accuracy was evaluated by concordance index, calibration curve, decision curve and clinical impact curve. Results: The neutrophil-to-lymphocyte ratio (NLR) was identified as the independent risk factor for severe illness in patients with 2019-nCoV infection. The NLR had a c-index of 0.807 (95% confidence interval, 0.676-0.38), the calibration curves fitted well, and the decision curve and clinical impact curve showed that the NLR had superior standardized net benefit. In addition, the incidence of severe illness was 9.1% in age ≥ 50 and NLR < 3.13 patients, and half of patients with age ≥ 50 and NLR ≥ 3.13 would develop severe illness. Based on the risk stratification of NLR with age, the study developed a 2019-nCoV pneumonia management process. Conclusions: The NLR was the early identification of risk factors for 2019-nCoV severe illness. Patients with age ≥ 50 and NLR ≥ 3.13 facilitated severe illness, and they should rapidly access to intensive care unit if necessary.

Use of the informational spectrum methodology for rapid biological analysis of the novel coronavirus 2019-nCoV: prediction of potential receptor, natural reservoir, tropism and therapeutic/vaccine target.

A novel coronavirus recently identified in Wuhan, China (2019-nCoV) has expanded the number of highly pathogenic coronaviruses affecting humans. The 2019-nCoV represents a potential epidemic or pandemic threat, which requires a quick response for preparedness against this infection. The present report uses the informational spectrum methodology to identify the possible origin and natural host of the new virus, as well as putative therapeutic and vaccine targets. The performed in silico analysis indicates that the newly emerging 2019-nCoV is closely related to severe acute respiratory syndrome (SARS)-CoV and, to a lesser degree, Middle East respiratory syndrome (MERS)-CoV. Moreover, the well-known SARS-CoV receptor (ACE2) might be a putative receptor for the novel virus as well. Actin protein was also suggested as a host factor that participates in cell entry and pathogenesis of 2019-nCoV; therefore, drugs modulating biological activity of this protein (e.g. ibuprofen) were suggested as potential candidates for treatment of this viral infection. Additional results indicated that civets and poultry are potential candidates for the natural reservoir of the 2019-nCoV, and that domain 288-330 of S1 protein from the 2019-nCoV represents promising therapeutic and/or vaccine target.

The digestive system is a potential route of 2019-nCov infection: a bioinformatics analysis based on single-cell transcriptomes

Since December 2019, a newly identified coronavirus (2019 novel coronavirus, 2019-nCov) is causing outbreak of pneumonia in one of largest cities, Wuhan, in Hubei province of China and has draw significant public health attention. The same as severe acute respiratory syndrome coronavirus (SARS-CoV), 2019-nCov enters into host cells via cell receptor angiotensin converting enzyme II (ACE2). In order to dissect the ACE2-expressing cell composition and proportion and explore a potential route of the 2019-nCov infection in digestive system infection, 4 datasets with single-cell transcriptomes of lung, esophagus, gastric, ileum and colon were analyzed. The data showed that ACE2 was not only highly expressed in the lung AT2 cells, esophagus upper and stratified epithelial cells but also in absorptive enterocytes from ileum and colon. These results indicated along with respiratory systems, digestive system is a potential routes for 2019-nCov infection. In conclusion, this study has provided the bioinformatics evidence of the potential route for infection of 2019-nCov in digestive system along with respiratory tract and may have significant impact for our healthy policy setting regards to prevention of 2019-nCoV infection.

Receptor Recognition by the Novel Coronavirus from Wuhan: an Analysis Based on Decade-Long Structural Studies of SARS Coronavirus

Recently, a novel coronavirus (2019-nCoV) has emerged from Wuhan, China, causing symptoms in humans similar to those caused by severe acute respiratory syndrome coronavirus (SARS-CoV). Since the SARS-CoV outbreak in 2002, extensive structural analyses have revealed key atomic-level interactions between the SARS-CoV spike protein receptor-binding domain (RBD) and its host receptor angiotensin-converting enzyme 2 (ACE2), which regulate both the cross-species and human-to-human transmissions of SARS-CoV. Here, we analyzed the potential receptor usage by 2019-nCoV, based on the rich knowledge about SARS-CoV and the newly released sequence of 2019-nCoV. First, the sequence of 2019-nCoV RBD, including its receptor-binding motif (RBM) that directly contacts ACE2, is similar to that of SARS-CoV, strongly suggesting that 2019-nCoV uses ACE2 as its receptor. Second, several critical residues in 2019-nCoV RBM (particularly Gln493) provide favorable interactions with human ACE2, consistent with 2019-nCoV's capacity for human cell infection. Third, several other critical residues in 2019-nCoV RBM (particularly Asn501) are compatible with, but not ideal for, binding human ACE2, suggesting that 2019-nCoV has acquired some capacity for human-to-human transmission. Last, while phylogenetic analysis indicates a bat origin of 2019-nCoV, 2019-nCoV also potentially recognizes ACE2 from a diversity of animal species (except mice and rats), implicating these animal species as possible intermediate hosts or animal models for 2019-nCoV infections. These analyses provide insights into the receptor usage, cell entry, host cell infectivity and animal origin of 2019-nCoV and may help epidemic surveillance and preventive measures against 2019-nCoV.IMPORTANCE The recent emergence of Wuhan coronavirus (2019-nCoV) puts the world on alert. 2019-nCoV is reminiscent of the SARS-CoV outbreak in 2002 to 2003. Our decade-long structural studies on the receptor recognition by SARS-CoV have identified key interactions between SARS-CoV spike protein and its host receptor angiotensin-converting enzyme 2 (ACE2), which regulate both the cross-species and human-to-human transmissions of SARS-CoV. One of the goals of SARS-CoV research was to build an atomic-level iterative framework of virus-receptor interactions to facilitate epidemic surveillance, predict species-specific receptor usage, and identify potential animal hosts and animal models of viruses. Based on the sequence of 2019-nCoV spike protein, we apply this predictive framework to provide novel insights into the receptor usage and likely host range of 2019-nCoV. This study provides a robust test of this reiterative framework, providing the basic, translational, and public health research communities with predictive insights that may help study and battle this novel 2019-nCoV.

[Progress and challenge of vaccine development against 2019 novel coronavirus (2019-nCoV)]

The outbreak of 2019 novel coronavirus (2019-nCoV) infection poses a serious threat to global public health. Vaccination is an effective way to prevent the epidemic of the virus. 2019-nCoV along with severe acute respiratory syndrome coronavirus (SARS-CoV) and Middle East respiratory syndrome coronavirus (MERS-CoV) belong to the same ß-genus of coronavirus family. Base on the previous experience and the technical platform of developing SARS-CoV and MERS-CoV vaccines, scientists from all over the world are working hard and quickly on the related fields. There are substantial progress in these fields including the characterizing the 2019-nCoV virus, identification of candidate antigens and epitopes, establishment of animal models, characterizing the immune responses, and the design of vaccines. The development of 2019-nCoV vaccines cover all types: inactivated virus vaccine, recombinant protein vaccine, viral vector-based vaccine, mRNA vaccine, and DNA vaccine, et al. As of March 2020, two 2019-nCoV vaccines have entered phase I clinical trials. One is named as Ad5-nCoV developed by the Chinese Institute of Biotechnology of the Academy of Military Medical Sciences and Tianjin Cansino Biotechnology Inc. Ad5-nCoV is based on the replication-defective adenovirus type 5 as the vector to express 2019-nCoV spike protein. The another vaccine is mRNA-1273 developed by the National Institute of Allergy and Infectious Diseases and Moderna, Inc.. RNA-1273 is an mRNA vaccine expressing 2019-nCoV spike protein. Although the rapid development of 2019-nCoV vaccine, it still faces many challenges with unknown knowledge, including the antigenic characteristics of the 2019-nCoV, the influence of antigenic variation, the protective immune response of host, the protection of the elderly population, and the downstream manufacturing process of the new vaccine. The safety and efficacy of vaccines are the first priority for vaccine development and should be carefully evaluated.

Recently, a novel coronavirus (2019-nCoV) has emerged from Wuhan, China, causing symptoms in humans similar to those caused by severe acute respiratory syndrome coronavirus (SARS-CoV). Since the SARS-CoV outbreak in 2002, extensive structural analyses have revealed key atomic-level interactions between the SARS-CoV spike protein receptor-binding domain (RBD) and its host receptor angiotensin-converting enzyme 2 (ACE2), which regulate both the cross-species and human-to-human transmissions of SARS-CoV. Here, we analyzed the potential receptor usage by 2019-nCoV, based on the rich knowledge about SARS-CoV and the newly released sequence of 2019-nCoV. First, the sequence of 2019-nCoV RBD, including its receptor-binding motif (RBM) that directly contacts ACE2, is similar to that of SARS-CoV, strongly suggesting that 2019-nCoV uses ACE2 as its receptor. Second, several critical residues in 2019-nCoV RBM (particularly Gln493) provide favorable interactions with human ACE2, consistent with 2019-nCoV’s capacity for human cell infection. Third, several other critical residues in 2019-nCoV RBM (particularly Asn501) are compatible with, but not ideal for, binding human ACE2, suggesting that 2019-nCoV has acquired some capacity for human-to-human transmission. Last, while phylogenetic analysis indicates a bat origin of 2019-nCoV, 2019-nCoV also potentially recognizes ACE2 from a diversity of animal species (except mice and rats), implicating these animal species as possible intermediate hosts or animal models for 2019-nCoV infections. These analyses provide insights into the receptor usage, cell entry, host cell infectivity and animal origin of 2019-nCoV and may help epidemic surveillance and preventive measures against 2019-nCoV. IMPORTANCE The recent emergence of Wuhan coronavirus (2019-nCoV) puts the world on alert. 2019-nCoV is reminiscent of the SARS-CoV outbreak in 2002 to 2003. Our decade-long structural studies on the receptor recognition by SARS-CoV have identified key interactions between SARS-CoV spike protein and its host receptor angiotensin-converting enzyme 2 (ACE2), which regulate both the cross-species and human-to-human transmissions of SARS-CoV. One of the goals of SARS-CoV research was to build an atomic-level iterative framework of virus-receptor interactions to facilitate epidemic surveillance, predict species-specific receptor usage, and identify potential animal hosts and animal models of viruses. Based on the sequence of 2019-nCoV spike protein, we apply this predictive framework to provide novel insights into the receptor usage and likely host range of 2019-nCoV. This study provides a robust test of this reiterative framework, providing the basic, translational, and public health research communities with predictive insights that may help study and battle this novel 2019-nCoV.

Predictions for the binding domain and potential new drug targets of 2019-nCoV

An outbreak of new SARS-like viral in Wuhan, China has been named 2019-nCoV. The current state of the epidemic is increasingly serious, and there has been the urgent necessity to develop an effective new drug. In previous studies, it was found that the conformation change in CTD1 was the region where SARS-CoV bound to human ACE2. Although there are mutations of the 2019-nCoV, the binding energy of ACE2 remains high. The surface glycoprotein of 2019-nCoV was coincident with the CTD1 region of the S-protein by comparing the I-TASSER prediction model with the actual SARS model, which suggests that 2019-nCoV may bind to the ACE2 receptor through conformational changes. Furthermore, site prediction on the surface glycoprotein of 2019-nCoV suggests some core amino acid area may be a novel drug target against 2019-nCoV.

2019-NCoV: What Every Neurologist Should Know?

The 2019 novel Corona Virus pandemic beginning from Wuhan, China primarily affects the respiratory tract but its has impacted clinical practice across a range of specialities including neurology. We review the bearing of the 2019 NCoV infection on neurological practice. Neurological manifestations are less common than respiratory manifestations, yet conspicuous, affecting nearly over a third of hospitalized individuals. These may be classified in to early – headache, dizziness, hyposmia and hypogeusia and late – encephalopathy. Rarely but surely, a very small proportion of infected individuals might present with stroke. Certain neurological conditions, including cerebrovascular disease in both China and Italy and dementia in Italy predispose to infection and more severe manifestations, requiring intensive care unit admission. There is no convincing evidence that the manifestations, course and outcome of various neurological disorders is impacted by 2019 nCoV infection. Concerns of an increased risk of febrile seizures offset by a reduced frequency of infection in the paediatric age group. Individuals with multiple sclerosis might potentially experience both true and pseudorelapses. Besides a direct effect, 2019 nCoV has tremendously affected neurological care by disrupting the continuity of care and the availability of neurological medicines worldwide. Neurologists should respond to this challenge by developing and sustaining innovative methods of providing care as well as alerting the society at large to adopt measures to contain the spread of 2019 nCoV.

Saliva: a diagnostic option and a transmission route for 2019-nCoV

Data sources This review included 13 clinical studies (observational or clinical trial) which reported results of studies of the 2019 novel coronavirus (2019-nCoV). The other 62 referenced papers were of different types (eg, reviews, WHO protocols, letter to editor etc).Study selection The study selected trials, reviews, and in-vitro research assessing the critical aspects of saliva as an easily accessible and early-stage diagnostic source, and also an entry route for 2019-nCoV. Most of the clinical studies were descriptive case series of patients who had contracted 2019-nCoV in China. These were mainly studies designed to compare saliva samples with throat swabs, with regard to the presence of 2019-nCoV RNA. Another aspect of the included studies was the susceptibility of oral tissues to 2019-nCoV due to the expression of angiotensin-converting enzyme II (ACE2) as a receptor for the 2019-nCoV. Some review studies and clinical infection control protocols were also included to discuss the transmission patterns of 2019-nCoV from the oral cavity. Studies were not restricted to English language and they were not all full-text papers.Data extraction and synthesis A narrative synthesis of the results was conducted using distinct headings and subheadings, defined by the authors based on relevancy to the consensus about the importance of saliva with reference to 2019-nCoV.Results There was an inherent heterogeneity among the included clinical studies concerning their designs, sampling techniques, and the results about the diagnostic value of saliva. The percentage of coronavirus disease of 2019 (COVID-19) patients with positive 2019-nCoV RNA varied from 12.9% to 91.67% among these studies. Regarding the possibility of direct virus invasion into the oral tissues, the results suggested that ACE2+ cells in salivary glands could possibly be the target cells of 2019-nCoV and theoretically could generate infectious saliva in a sustained way. Furin was suggested as another protein which makes the tongue more vulnerable to 2019-nCoV, especially in conditions inducing its upregulation (for example, squamous cell carcinoma). According to the comparisons between 2019-nCoV and SARS-CoV, saliva could be considered of diagnostic value via the early detection of viral RNA for both of the viruses. Whilst the viral peak was shown to be at onset of symptoms for 2019-nCoV, it can linger up to the tenth day after the appearance of symptoms for SARS-CoV. Finally, this paper warns about airborne transmission, particularly for close contacts.Conclusions Saliva can be proposed as an easily accessible diagnostic source although further clinical studies are required. Given the presence of viral RNA in saliva in the early stages of COVID-19, the recommendations to wear masks to prevent the rapid transmission of infectious droplets into the air, and keep a safe distance from other people are clearly based in evidence.

Data sources This review included 13 clinical studies (observational or clinical trial) which reported results of studies of the 2019 novel coronavirus (2019-nCoV). The other 62 referenced papers were of different types (eg, reviews, WHO protocols, letter to editor etc). Study selection The study selected trials, reviews, and in-vitro research assessing the critical aspects of saliva as an easily accessible and early-stage diagnostic source, and also an entry route for 2019-nCoV. Most of the clinical studies were descriptive case series of patients who had contracted 2019-nCoV in China. These were mainly studies designed to compare saliva samples with throat swabs, with regard to the presence of 2019-nCoV RNA. Another aspect of the included studies was the susceptibility of oral tissues to 2019-nCoV due to the expression of angiotensin-converting enzyme II (ACE2) as a receptor for the 2019-nCoV. Some review studies and clinical infection control protocols were also included to discuss the transmission patterns of 2019-nCoV from the oral cavity. Studies were not restricted to English language and they were not all full-text papers. Data extraction and synthesis A narrative synthesis of the results was conducted using distinct headings and subheadings, defined by the authors based on relevancy to the consensus about the importance of saliva with reference to 2019-nCoV. Results There was an inherent heterogeneity among the included clinical studies concerning their designs, sampling techniques, and the results about the diagnostic value of saliva. The percentage of coronavirus disease of 2019 (COVID-19) patients with positive 2019-nCoV RNA varied from 12.9% to 91.67% among these studies. Regarding the possibility of direct virus invasion into the oral tissues, the results suggested that ACE2+ cells in salivary glands could possibly be the target cells of 2019-nCoV and theoretically could generate infectious saliva in a sustained way. Furin was suggested as another protein which makes the tongue more vulnerable to 2019-nCoV, especially in conditions inducing its upregulation (for example, squamous cell carcinoma). According to the comparisons between 2019-nCoV and SARS-CoV, saliva could be considered of diagnostic value via the early detection of viral RNA for both of the viruses. Whilst the viral peak was shown to be at onset of symptoms for 2019-nCoV, it can linger up to the tenth day after the appearance of symptoms for SARS-CoV. Finally, this paper warns about airborne transmission, particularly for close contacts. Conclusions Saliva can be proposed as an easily accessible diagnostic source although further clinical studies are required. Given the presence of viral RNA in saliva in the early stages of COVID-19, the recommendations to wear masks to prevent the rapid transmission of infectious droplets into the air, and keep a safe distance from other people are clearly based in evidence.

Host and infectivity prediction of Wuhan 2019 novel coronavirus using deep learning algorithm

The recent outbreak of pneumonia in Wuhan, China caused by the 2019 Novel Coronavirus (2019-nCoV) emphasizes the importance of detecting novel viruses and predicting their risks of infecting people. In this report, we introduced the VHP (Virus Host Prediction) to predict the potential hosts of viruses using deep learning algorithm. Our prediction suggests that 2019-nCoV has close infectivity with other human coronaviruses, especially the severe acute respiratory syndrome coronavirus (SARS-CoV), Bat SARS-like Coronaviruses and the Middle East respiratory syndrome coronavirus (MERS-CoV). Based on our prediction, compared to the Coronaviruses infecting other vertebrates, bat coronaviruses are assigned with more similar infectivity patterns with 2019-nCoVs. Furthermore, by comparing the infectivity patterns of all viruses hosted on vertebrates, we found mink viruses show a closer infectivity pattern to 2019-nCov. These consequences of infectivity pattern analysis illustrate that bat and mink may be two candidate reservoirs of 2019-nCov.These results warn us to beware of 2019-nCoV and guide us to further explore the properties and reservoir of it. It is of great value to identify whether a newly discovered virus has the risk of infecting human. Guo et al. proposed a virus host prediction method based on deep learning to detect what kind of host a virus can infect with DNA sequence as input. Applied to the Wuhan 2019 Novel Coronavirus, our prediction demonstrated that several vertebrate-infectious coronaviruses have strong potential to infect human. This method will be helpful in future viral analysis and early prevention and control of viral pathogens.

[Progress and challenge of vaccine development against 2019 novel coronavirus (2019-nCoV)].

The outbreak of 2019 novel coronavirus (2019-nCoV) infection poses a serious threat to global public health. Vaccination is an effective way to prevent the epidemic of the virus. 2019-nCoV along with severe acute respiratory syndrome coronavirus (SARS-CoV) and Middle East respiratory syndrome coronavirus (MERS-CoV) belong to the same β-genus of coronavirus family. Base on the previous experience and the technical platform of developing SARS-CoV and MERS-CoV vaccines, scientists from all over the world are working hard and quickly on the related fields. There are substantial progress in these fields including the characterizing the 2019-nCoV virus, identification of candidate antigens and epitopes, establishment of animal models, characterizing the immune responses, and the design of vaccines. The development of 2019-nCoV vaccines cover all types: inactivated virus vaccine, recombinant protein vaccine, viral vector-based vaccine, mRNA vaccine, and DNA vaccine, et al. As of March 2020, two 2019-nCoV vaccines have entered phase I clinical trials. One is named as Ad5-nCoV developed by the Chinese Institute of Biotechnology of the Academy of Military Medical Sciences and Tianjin Cansino Biotechnology Inc. Ad5-nCoV is based on the replication-defective adenovirus type 5 as the vector to express 2019-nCoV spike protein. The another vaccine is mRNA-1273 developed by the National Institute of Allergy and Infectious Diseases and Moderna, Inc.. RNA-1273 is an mRNA vaccine expressing 2019-nCoV spike protein. Although the rapid development of 2019-nCoV vaccine, it still faces many challenges with unknown knowledge, including the antigenic characteristics of the 2019-nCoV, the influence of antigenic variation, the protective immune response of host, the protection of the elderly population, and the downstream manufacturing process of the new vaccine. The safety and efficacy of vaccines are the first priority for vaccine development and should be carefully evaluated.

Analysis of codon usage and evolutionary rates of the 2019-nCoV genes

Severe acute respiratory syndrome coronavirus 2 (2019-nCoV), which first broke out in Wuhan (China) in December of 2019, causes a severe acute respiratory illness with a mortality ranging from 3% to 6%. To better understand the evolution of the newly emerging 2019-nCoV, in this paper, we analyze the codon usage pattern of 2019-nCoV. For this purpose, we compare the codon usage of 2019-nCoV with that of other 30 viruses belonging to the subfamily of orthocoronavirinae. We found that 2019-nCoV shows a rich composition of AT nucleotides that strongly influences its codon usage, which appears to be not optimized to human host. Then, we study the evolutionary pressures influencing the codon usage and evolutionary rates of the sequences of five conserved genes that encode the corresponding proteins (viral replicase, spike, envelope, membrane and nucleocapsid) characteristic of coronaviruses. We found different patterns of both mutational bias and nature selection that affect the codon usage of these genes at different extents. Moreover, we show that the two integral membrane proteins proteins (matrix and envelope) tend to evolve slowly by accumulating nucleotide mutations on their genes. Conversely, genes encoding nucleocapsid (N), viral replicase and spike proteins are important targets for the development of vaccines and antiviral drugs, tend to evolve faster as compared to other ones. Taken together, our results suggest that the higher evolutionary rate observed for these two genes could represent a major barrier in the development of antiviral therapeutics 2019-nCoV.

Environmental concern regarding the effect of humidity and temperature on 2019-nCoV survival: fact or fiction

The new coronavirus, called 2019-nCoV, is a new type of virus that was first identified in Wuhan, China, in December 2019. Environmental conditions necessary for survival and spread of 2019-nCoV are somewhat transparent but unlike animal coronaviruses. We are poorly aware of their survival in environment and precise factors of their transmission. Countries located in east and west of globe did not have a significant impact on prevalence of disease among communities, and on the other hand, north and south have provided a model for relative prediction of disease outbreaks. The 2019-nCoV can survive for up to 9 days at 25 °C, and if this temperature rises to 30 °C, its lifespan will be shorter. The 2019-nCoV is sensitive to humidity, and lifespan of viruses in 50% humidity is longer than that of 30%. Also, temperature and humidity are important factors influencing the COVID-19 mortality rate and may facilitate 2019-nCoV transmission. Thus, considering the available and recent evidence, it seems that low temperatures, as well as dry and unventilated air, may affect stability and transmissibility of 2019-nCoV.

2019-nCoV - Towards a 4th generation vaccine

The first report of the unusual manifestation of pneumonia-like symptoms in Wuhan City, China was made on 31 December 2019. Within one week, the Chinese authorities reported that they had identified the causative agent as a new member of the Coronavirus family, the same family of that was responsible for MERS and SARS not so many years ago. The new virus was called Novel Coronavirus 2019 (2019-nCoV). Three weeks later, the World Health Organization declared that 2019-nCoV was capable of direct human-to-human transmission, the virus had spread across several countries in three continents, and had infected close to two thousand people, of whom at least 1 in 5 quite severely. The number of fatalities was fast rising. Yet, the World Health Organization officially announced that there is still at present no recommended anti-nCoV vaccine for subject at-risk, nor treatment for patients with suspected or confirmed nCoV, let alone 2019-nCov. It is therefore timely and critical to propose new possible and practical approaches for preventive interventions for subjects at-risk, and for treatment of patients afflicted with 2019-nCov-induced disease (Corona Virus Disease 2019; COVID-19) before the present situation explodes into a worldwide pandemic. One such potential clinical protocol is proposed as a hypothesis.

A comparative study on the clinical features of COVID-19 pneumonia to other pneumonias

BACKGROUND: A novel coronavirus (2019-nCoV) has raised world concern since it emerged in Wuhan Hubei China in December, 2019. The infection may result into severe pneumonia with clusters illness onsets. Its impacts on public health make it paramount to clarify the clinical features with other pneumonias. METHODS: Nineteen 2019-nCoV pneumonia (NCOVID-19) and fifteen other pneumonia patients (NON-NCOVID-19) in out of Hubei places were involved in this study. Both NCOVID-19 and NON-NCOVID-19 patients were confirmed to be infected in throat swabs or/and sputa with or without 2019-nCoV by real-time RT-PCR. We analyzed the demographic, epidemiological, clinical, and radiological features from those patients, and compared the difference between NCOVID-19 and NON-NCOVID-19. RESULTS: All patients had a history of exposure to confirmed case of 2019-nCoV or travel to Hubei before illness. The median duration, respectively, was 8 (IQR:6~11) and 5 (IQR:4~11) days from exposure to onset in NCOVID-19 and NON-NCOVID-19. The clinical symptoms were similar between NCOVID-19 and NON-NCOVID-19. The most common symptoms were fever and cough. Fifteen (78.95%) NCOVID-19 but 4 (26.67%) NON-NCOVID-19 patients had bilateral involvement while 17 (89.47%) NCOVID-19 but 1 (6.67%) NON-NCOVID-19 patients had multiple mottling and ground-glass opacity of chest CT images. Compared to NON-NCOVID-19, NCOVID-19 present remarkably more abnormal laboratory tests including AST, ALT, γ-GT, LDH and α-HBDH. CONCLUSION: The 2019-nCoV infection caused similar onsets to other pneumonias. CT scan may be a reliable test for screening NCOVID-19 cases. Liver function damage is more frequent in NCOVID-19 than NON-NCOVID-19 patients. LDH and α-HBDH may be considerable markers for evaluation of NCOVID-19.

2019 novel coronavirus (2019-nCoV) and 2019-nCoV pneumonia/ 中华微生物学和免疫学杂志

In the middle of December in 2019, a pneumonia outbreak caused by a new coronavirus, 2019 novel coronavirus (2019-nCoV), emerged in the populations in Wuhan city of China. The epidemic spreads rapidly and has been disseminated throughout the country and to 13 other counties in Asia, Europe, Oceania and North America. To accurately and deeply understand the biological characteristics, epidemiological features and pathogenicity of 2019-nCoV and related immunological characteristics, microbiological examinations and public protection measure, this study reviewed 2019-nCoV and 2019-nCoV pneumonia based on the newest relevant literatures and the newest version of National Diagnosis and Treatment Scheme of 2019-nCoV pneumonia.

A novel coronavirus recently identified in Wuhan, China (2019-nCoV) has expanded the number of highly pathogenic coronaviruses affecting humans. The 2019-nCoV represents a potential epidemic or pandemic threat, which requires a quick response for preparedness against this infection. The present report uses the informational spectrum methodology to identify the possible origin and natural host of the new virus, as well as putative therapeutic and vaccine targets. The performed in silico analysis indicates that the newly emerging 2019-nCoV is closely related to severe acute respiratory syndrome (SARS)-CoV and, to a lesser degree, Middle East respiratory syndrome (MERS)-CoV. Moreover, the well-known SARS-CoV receptor (ACE2) might be a putative receptor for the novel virus as well. Additional results indicated that civets and poultry are potential candidates for the natural reservoir of the 2019-nCoV, and that domain 288-330 of S1 protein from the 2019-nCoV represents promising therapeutic and/or vaccine target.

BACKGROUND: A novel coronavirus (2019-nCoV) has raised world concern since it emerged in Wuhan Hubei China in December, 2019. The infection may result into severe pneumonia with clusters illness onsets. Its impacts on public health make it paramount to clarify the clinical features with other pneumonias. METHODS: Nineteen 2019-nCoV pneumonia (NCOVID-19) and fifteen other pneumonia patients (NON-NCOVID-19) in out of Hubei places were involved in this study. Both NCOVID-19 and NON-NCOVID-19 patients were confirmed to be infected in throat swabs or/and sputa with or without 2019-nCoV by real-time RT-PCR. We analyzed the demographic, epidemiological, clinical, and radiological features from those patients, and compared the difference between NCOVID-19 and NON-NCOVID-19. RESULTS: All patients had a history of exposure to confirmed case of 2019-nCoV or travel to Hubei before illness. The median duration, respectively, was 8 (IQR:6~11) and 5 (IQR:4~11) days from exposure to onset in NCOVID-19 and NON-NCOVID-19. The clinical symptoms were similar between NCOVID-19 and NON-NCOVID-19. The most common symptoms were fever and cough. Fifteen (78.95%) NCOVID-19 but 4 (26.67%) NON-NCOVID-19 patients had bilateral involvement while 17 (89.47%) NCOVID-19 but 1 (6.67%) NON-NCOVID-19 patients had multiple mottling and ground-glass opacity of chest CT images. Compared to NON-NCOVID-19, NCOVID-19 present remarkably more abnormal laboratory tests including AST, ALT, Î³-GT, LDH and α-HBDH. CONCLUSION: The 2019-nCoV infection caused similar onsets to other pneumonias. CT scan may be a reliable test for screening NCOVID-19 cases. Liver function damage is more frequent in NCOVID-19 than NON-NCOVID-19 patients. LDH and α-HBDH may be considerable markers for evaluation of NCOVID-19.

Persons Evaluated for 2019 Novel Coronavirus - United States, January 2020

In December 2019, a cluster of cases of pneumonia emerged in Wuhan City in central China's Hubei Province. Genetic sequencing of isolates obtained from patients with pneumonia identified a novel coronavirus (2019-nCoV) as the etiology (1). As of February 4, 2020, approximately 20,000 confirmed cases had been identified in China and an additional 159 confirmed cases in 23 other countries, including 11 in the United States (2,3). On January 17, CDC and the U.S. Department of Homeland Security's Customs and Border Protection began health screenings at U.S. airports to identify ill travelers returning from Wuhan City (4). CDC activated its Emergency Operations Center on January 21 and formalized a process for inquiries regarding persons suspected of having 2019-nCoV infection (2). As of January 31, 2020, CDC had responded to clinical inquiries from public health officials and health care providers to assist in evaluating approximately 650 persons thought to be at risk for 2019-nCoV infection. Guided by CDC criteria for the evaluation of persons under investigation (PUIs) (5), 210 symptomatic persons were tested for 2019-nCoV; among these persons, 148 (70%) had travel-related risk only, 42 (20%) had close contact with an ill laboratory-confirmed 2019-nCoV patient or PUI, and 18 (9%) had both travel- and contact-related risks. Eleven of these persons had laboratory-confirmed 2019-nCoV infection. Recognizing persons at risk for 2019-nCoV is critical to identifying cases and preventing further transmission. Health care providers should remain vigilant and adhere to recommended infection prevention and control practices when evaluating patients for possible 2019-nCoV infection (6). Providers should consult with their local and state health departments when assessing not only ill travelers from 2019-nCoV-affected countries but also ill persons who have been in close contact with patients with laboratory-confirmed 2019-nCoV infection in the United States.

Diarrhea may be underestimated: a missing link in 2019 novel coronavirus

The outbreak of pneumonia caused by the 2019 Novel Coronavirus (2019-nCoV) was reported in Wuhan City, China. However, the clinical symptoms varied in different reports. Based on the results of inter-group difference test, we found that the incidence of diarrhea differed in three recent reports. As 2019-nCoV utilizes the same cell entry receptor ACE2 as severe acute respiratory syndrome coronavirus (SARS-CoV) and ACE2 tightly controls intestinal inflammation, to trace the route of infection mediated by 2019-nCoV, we used the single-cell RNA sequencing data for analysis. We found that the ACE2 mRNA was highly expressed in the healthy human small intestine rather than the lung. Besides, single-cell RNA sequencing data showed that ACE2 was significantly elevated in the proximal and distal enterocytes, where the small intestinal epithelium is exposed to the foreign pathogen. Thus, we suspect that ACE2-expressing small intestinal epithelium cells might be vulnerable to 2019-nCoV infection when people eat infected wild animals and diarrhea may serve as an indicator for infection, suggesting that clinicians should pay more attention to patients with diarrhea during the outbreak of pneumonia.

The diagnostic value of joint detection of serum IgMand IgG antibodies to 2019-nCoV in 2019-nCoV infection/ 中华检验医学杂志

Objective@#To investigate the diagnostic value of immunoglobulin M (IgM) and immunoglobulin G(IgG) antibodies to 2019 Novel Coronavirus (2019-nCoV) in 2019-nCoV infection.@*Method@#This is a retrospective study. Serum samples were collected from 284 patients including outpatients and inpatients in the Renmin Hospital of Wuhan University from January 20, 2020 to February 17, 2020. Among them 205 cases were 2019-nCoV infected patients, including 186 cases confirmed with nucleic acid test and 19 cases diagnosed by clinical symptoms and CT characteristics according to "the New Coronavirus Pneumonia Control Protocol (5th edition)" . A total of 79 subjects with other diseases but negative to 2019-nCoV infection were recruited as control group. Serum IgM and IgG antibodies to 2019-nCoV were measured with fully automated immunoassay technology for all subjects. Statistical significance between 2019-nCoV antibodies test and 2019-nCoV nucleic acid test was determined using the χ2 tests.@*Result@#The sensitivity of serum IgM and IgG antibodies to 2019-nCoV were 70.24%(144/205) and 96.10%(197/205) respectively and the specificity were 96.20%(76/79) and 92.41%(73/79) respectively. The positive and negative predictive values of 2019-nCoV antibodies were 95.63%(197/206) and 91.03% (71/78) respectively, and the positive and negative predictive values of 2019-nCoV nucleic acid test were 100%(186/186) and 80.61%(79/98) respectively. The total coincidence rate of diagnosing 2019-nCoV infection between antibody tests and nucleic acid test for 2019-nCoV were 88.03%(250/284).@*Conclusion@#Joint detection of serum IgM and IgG antibodies to 2019-nCoV is an effective screening and diagnostic indicators for 2019-nCoV infection, and an effective complement to the false negative results to nucleic acid test.

Persons Evaluated for 2019 Novel Coronavirus — United States, January 2020

Cryo-EM structure of the 2019-nCoV spike in the prefusion conformation

The outbreak of a novel coronavirus (2019-nCoV) represents a pandemic threat that has been declared a public health emergency of international concern. The CoV spike (S) glycoprotein is a key target for vaccines, therapeutic antibodies, and diagnostics. To facilitate medical countermeasure development, we determined a 3.5-angstrom-resolution cryo-electron microscopy structure of the 2019-nCoV S trimer in the prefusion conformation. The predominant state of the trimer has one of the three receptor-binding domains (RBDs) rotated up in a receptor-accessible conformation. We also provide biophysical and structural evidence that the 2019-nCoV S protein binds angiotensin-converting enzyme 2 (ACE2) with higher affinity than does severe acute respiratory syndrome (SARS)-CoV S. Additionally, we tested several published SARS-CoV RBD-specific monoclonal antibodies and found that they do not have appreciable binding to 2019-nCoV S, suggesting that antibody cross-reactivity may be limited between the two RBDs. The structure of 2019-nCoV S should enable the rapid development and evaluation of medical countermeasures to address the ongoing public health crisis.

The outbreak of a novel coronavirus (2019-nCoV) represents a pandemic threat that has been declared a public health emergency of international concern. The CoV spike (S) glycoprotein is a key target for vaccines, therapeutic antibodies, and diagnostics. To facilitate medical countermeasure development, we determined a 3.5-angstrom-resolution cryo–electron microscopy structure of the 2019-nCoV S trimer in the prefusion conformation. The predominant state of the trimer has one of the three receptor-binding domains (RBDs) rotated up in a receptor-accessible conformation. We also provide biophysical and structural evidence that the 2019-nCoV S protein binds angiotensin-converting enzyme 2 (ACE2) with higher affinity than does severe acute respiratory syndrome (SARS)-CoV S. Additionally, we tested several published SARS-CoV RBD-specific monoclonal antibodies and found that they do not have appreciable binding to 2019-nCoV S, suggesting that antibody cross-reactivity may be limited between the two RBDs. The structure of 2019-nCoV S should enable the rapid development and evaluation of medical countermeasures to address the ongoing public health crisis.

[2019-nCoV: new challenges from coronavirus]

The outbreak of pneumonia caused by the novel coronavirus 2019-nCoV in Wuhan, Hubei province of China, at the end of 2019 shaped tremendous challenges to China's public health and clinical treatment. The virus belongs to the ß genus Coronavirus in the family Corornaviridae, and is closely related to SARS-CoV and MERS-CoV, causing severe symptoms of pneumonia. The virus is transmitted through droplets, close contact, and other means, and patients in the incubation period could potentially transmit the virus to other persons. According to current observations, 2019-nCoV is weaker than SARS in pathogenesis, but has stronger transmission competence; it's mechanism of cross-species spread might be related with angiotensin-converting enzyme â ¡ (ACE2), which is consistent with the receptor SARS-CoV. After the outbreak of this disease, Chinese scientists invested a lot of energy to carry out research by developing rapid diagnostic reagents, identifying the characters of the pathogen, screening out clinical drugs that may inhibit the virus, and are rapidly developing vaccines. The emergence of 2019-nCoV reminds us once again of the importance of establishing a systematic coronavirus surveillance network. It also poses new challenges to prevention and control of the emerging epidemic and rapidly responses on scientific research.

[2019-nCoV: new challenges from coronavirus].

The outbreak of pneumonia caused by the novel coronavirus (2019-nCoV) in Wuhan, Hubei province of China, at the end of 2019 shaped tremendous challenges to China's public health and clinical treatment. The virus belongs to the β genus Coronavirus in the family Corornaviridae, and is closely related to SARS-CoV and MERS-CoV, causing severe symptoms of pneumonia. The virus is transmitted through droplets, close contact, and other means, and patients in the incubation period could potentially transmit the virus to other persons. According to current observations, 2019-nCoV is weaker than SARS in pathogenesis, but has stronger transmission competence; it's mechanism of cross-species spread might be related with angiotensin-converting enzyme Ⅱ (ACE2), which is consistent with the receptor SARS-CoV. After the outbreak of this disease, Chinese scientists invested a lot of energy to carry out research by developing rapid diagnostic reagents, identifying the characters of the pathogen, screening out clinical drugs that may inhibit the virus, and are rapidly developing vaccines. The emergence of 2019-nCoV reminds us once again of the importance of establishing a systematic coronavirus surveillance network. It also poses new challenges to prevention and control of the emerging epidemic and rapidly responses on scientific research.

Remdesivir (GS-5734) as a therapeutic option of 2019-nCOV main protease – in silico approach

2019 – Novel Coronavirus (2019-nCOV), enclosed large genome positive-sense RNA virus characterized by crown-like spikes that protrude from their surface, and have a distinctive replication strategy. The 2019-nCOV belongs to the Coronaviridae family, principally consists of virulent pathogens showing zoonotic property, has emerged as a pandemic outbreak with high mortality and high morbidity rate around the globe and no therapeutic vaccine or drugs against 2019-nCoV are discovered till now. In this study, in silico methods and algorithms were used for sequence, structure analysis and molecular docking on M(pro) of 2019-nCOV. The co-crystal structure of 2019-nCOV protease, 6LU7 have ∼99% identity with SARS-CoV protease. The 6LU7 residues, Cys145 and His164 are playing a significant role in replication and are essential for the survival of 2019-nCOV. Alongside, 2019-nCOV M(pro) sequence is non-homologous to human host-pathogen. Complete genome sequence analysis, structural and molecular docking results revealed that Remdesivir is having a better binding affinity with -8.2 kcal/mol than the rest of protease inhibitors, and peptide. Remdesivir is strongly forming h-bonds with crucial M(pro) residues, Cys145, and His164. Further, MD simulation analysis also confirmed, that these residues are forming H-bond with Remdesivir during 100 ns simulations run and found stable (∼99%) by RMSD and RMSF. Thus, present in silico study at molecular approaches suggest that, Remdesivir is a potent therapeutic inhibitor against 2019-nCoV. Communicated by Ramaswamy H. Sarma

Clinical diagnosis of 8274 samples with 2019-novel coronavirus in Wuhan

Background: 2019-Novel coronavirus (2019-nCoV) outbreaks create challenges for hospital laboratories because thousands of samples must be evaluated each day. Sample types, interpretation methods, and corresponding laboratory standards must be established. The possibility of other infections should be assessed to provide a basis for clinical classification, isolation, and treatment. Accordingly, in the present study, we evaluated the testing methods for 2019-nCoV and co-infections. Methods: We used a fluorescence-based quantitative PCR kit urgently distributed by the Chinese CDC to detect 8274 close contacts in the Wuhan region against two loci on the 2019-nCoV genome. We also analyzed 613 patients with fever who underwent multiple tests for 13 respiratory pathogens; 316 subjects were also tested for 2019-nCoV. Findings: Among the 8274 subjects, 2745 (33.2%) had 2019-nCoV infection; 5277 (63.8%) subjects showed negative results in the 2019-nCoV nucleic acid test (non-019-nCoV); and 252 cases (3.0%) because only one target was positive, the diagnosis was not definitive. Sixteen patients who originally had only one positive target were re-examined a few days later; 14 patients (87.5%) were finally defined as 2019-nCoV-positive, and 2 (12.5%) were finally defined as negative. The positive rates of nCoV-NP and nCovORF1ab were 34.7% and 34.7%, respectively. nCoV-NP-positive only and nCovORF1ab-positive cases accounted for 1.5% and 1.5%, respectively. In the 316 patients with multiple respiratory pathogens, 104 were positive for 2019-nCov and 6/104 had co-infection with coronavirus (3/104), influenza A virus (2/104), rhinovirus (2/104), and influenza A H3N2 (1/104); the remaining 212 patients had influenza A virus (11/202), influenza A H3N2 (11/202), rhinovirus (10/202), respiratory syncytial virus (7/202), influenza B virus (6/202), metapneumovirus (4/202), and coronavirus (2/202). Interpretation: Clinical testing methods for 2019-nCoV require improvement. Importantly, 5.8% of 2019-nCoV infected and 18.4% of non-2019-nCoV-infected patients had other pathogen infections. It is important to treat combined infections and perform rapid screening to avoid cross-contamination of patients. A test that quickly and simultaneously screens as many pathogens as possible is needed.

Prediction of numbers of the accumulative confirmed patients (NACP) and the plateau phase of 2019-nCoV in China

In the present study, I propose a novel fitting method to describe the outbreak of 2019-nCoV in China. The fitted data were selected carefully from the non-Hubei part and Hubei Province of China respectively. For the non-Hubei part, the time period of data collection corresponds from the beginning of the policy of isolation to present day. But for Hubei Province, the subjects of Wuhan City and Hubei Province were included from the time of admission to the Huoshenshan Hospital to present day in order to ensure that all or the majority of the confirmed and suspected patients were collected for diagnosis and treatment. The employed basic functions for fitting are the hyperbolic tangent functions tanh ( . ) since in these cases the 2019-nCoV is just an epidemic. Subsequently, the 2019-nCoV will initially expand rapidly and tend to disappear. Therefore, the numbers of the accumulative confirmed patients in different cities, provinces and geographical regions will initially increase rapidly and subsequently stabilize to a plateau phase. The selection of the basic functions for fitting is crucial. In the present study, I found that the hyperbolic tangent functions tanh ( . ) could satisfy the aforementioned properties. By this novel method, I can obtain two significant results. They base on the conditions that the rigorous isolation policy is executed continually. Initially, I can predict the numbers very accurately of the cumulative confirmed patients in different cities, provinces and parts in China, notably, in Wuhan City with the smallest relative error estimated to 0.021 % , in Hubei Province with the smallest relative error estimated to 0.012 % and in the non-Hubei part of China with the smallest relative error of - 0.195% in the short-term period of infection. In addition, perhaps I can predict the times when the plateau phases will occur respectively in different regions in the long-term period of infection. Generally for the non-Hubei part of China, the plateau phase of the outbreak of the 2019-nCoV will be expected this March or at the end of this February. In the non-Hubei region of China it is expected that the epidemic will cease on the 30th of March 2020 and following this date no new confirmed patient will be expected. The predictions of the time of Inflection Points and maximum NACP for some important regions may be also obtained. A specific plan for the prevention measures of the 2019-nCoV outbreak must be implemented. This will involve the present returning to work and resuming production in China. Based on the presented results, I suggest that the rigorous isolation policy by the government should be executed regularly during daily life and work duties. Moreover, as many as possible the confirmed and suspected cases should be collected to diagnose or treat.

Use of the informational spectrum methodology for rapid biological analysis of the novel coronavirus 2019-nCoV: prediction of potential receptor, natural reservoir, tropism and therapeutic/vaccine target

Profiling ACE2 expression in colon tissue of healthy adults and colorectal cancer patients by single-cell transcriptome analysis

A newly identified novel coronavirus (2019-nCoV) has caused numerous acute respiratory syndrome cases in Wuhan China from December 2019 to Feb 2020. Its fast spreading to other provinces in China and overseas is very likely causing a pandemic. Since the novel coronavirus has been reported to be capable of endangering thousands of lives, it is extremely important to find out how the coronavirus is transmitted in human organs. Apart from fever and respiratory complications, gastrointestinal symptoms are observed in some patients with 2019-nCoV but the significance remains undetermined. The cell receptor angiotensin covering enzyme II (ACE2), which is the major receptor of SARS-nCoV, has been reported to be a cellular entry receptor of 2019-nCoV as well. Here, to more precisely explore the potential pathogen transmission route of the 2019-nCoV infections in the gastrointestinal tract, we analyzed the ACE2 RNA expression profile in the colon tissue of healthy adults and colorectal cancer patients of our cohort and other databases. The data indicates that ACE2 is mainly expressed in epithelial cells of the colon. The expression of ACE2 is gradually increased from healthy control, adenoma to colorectal cancer patients in our cohort as well as in the external Asian datasets. According to the expression profile of ACE2 in colon epithelial cells, we speculate adenoma and colorectal cancer patients are more likely to be infected with 2019-nCoV than healthy people. Our data may provide a theoretical basis for the classification and management of future 2019-nCoV susceptibility people in clinical application.

Saliva: potential diagnostic value and transmission of 2019-nCoV

2019-nCoV epidemic was firstly reported at late December of 2019 and has caused a global outbreak of COVID-19 now. Saliva, a biofluid largely generated from salivary glands in oral cavity, has been reported 2019-nCoV nucleic acid positive. Besides lungs, salivary glands and tongue are possibly another hosts of 2019-nCoV due to expression of ACE2. Close contact or short-range transmission of infectious saliva droplets is a primary mode for 2019-nCoV to disseminate as claimed by WHO, while long-distance saliva aerosol transmission is highly environment dependent within indoor space with aerosol-generating procedures such as dental practice. So far, no direct evidence has been found that 2019-nCoV is vital in air flow for long time. Therefore, to prevent formation of infectious saliva droplets, to thoroughly disinfect indoor air and to block acquisition of saliva droplets could slow down 2019-nCoV dissemination. This review summarizes diagnostic value of saliva for 2019-nCoV, possibly direct invasion into oral tissues, and close contact transmission of 2019-nCoV by saliva droplets, expecting to contribute to 2019-nCoV epidemic control.

Detectable 2019-nCoV viral RNA in blood is a strong indicator for the further clinical severity

The novel coronavirus (2019-nCoV) infection caused pneumonia. we retrospectively analyzed the virus presence in the pharyngeal swab, blood, and the anal swab detected by real-time PCR in the clinical lab. Unexpectedly, the 2109-nCoV RNA was readily detected in the blood (6 of 57 patients) and the anal swabs (11 of 28 patients). Importantly, all of the 6 patients with detectable viral RNA in the blood cohort progressed to severe symptom stage, indicating a strong correlation of serum viral RNA with the disease severity (p-value = 0.0001). Meanwhile, 8 of the 11 patients with annal swab virus-positive was in severe clinical stage. However, the concentration of viral RNA in the anal swab (Ct value = 24 + 39) was higher than in the blood (Ct value = 34 + 39) from patient 2, suggesting that the virus might replicate in the digestive tract. Altogether, our results confirmed the presence of virus RNA in extra-pulmonary sites.

Increasing Host Cellular Receptor—Angiotensin-Converting Enzyme 2 (ACE2) Expression by Coronavirus may Facilitate 2019-nCoV Infection

The ongoing outbreak of a new coronavirus (2019-nCoV) causes an epidemic of acute respiratory syndrome in humans. 2019-nCoV rapidly spread to national regions and multiple other countries, thus, pose a serious threat to public health. Recent studies show that spike (S) proteins of 2019-nCoV and SARS-CoV may use the same host cell receptor called angiotensin-converting enzyme 2 (ACE2) for entering into host cells. The affinity between ACE2 and 2019-nCoV S is much higher than ACE2 binding to SARS-CoV S protein, explaining that why 2019-nCoV seems to be more readily transmitted from the human to human. Here, we reported that ACE2 can be significantly upregulated after infection of various viruses including SARS-CoV and MERS-CoV. Basing on findings here, we propose that coronavirus infection can positively induce its cellular entry receptor to accelerate their replication and spread, thus drugs targeting ACE2 expression may be prepared for the future emerging infectious diseases caused by this cluster of viruses.

The outbreak of pneumonia caused by the novel coronavirus 2019-nCoV in Wuhan, Hubei province of China, at the end of 2019 shaped tremendous challenges to China's public health and clinical treatment. The virus belongs to the β genus Coronavirus in the family Corornaviridae, and is closely related to SARS-CoV and MERS-CoV, causing severe symptoms of pneumonia. The virus is transmitted through droplets, close contact, and other means, and patients in the incubation period could potentially transmit the virus to other persons. According to current observations, 2019-nCoV is weaker than SARS in pathogenesis, but has stronger transmission competence; it's mechanism of cross-species spread might be related with angiotensin-converting enzyme Ⅱ (ACE2), which is consistent with the receptor SARS-CoV. After the outbreak of this disease, Chinese scientists invested a lot of energy to carry out research by developing rapid diagnostic reagents, identifying the characters of the pathogen, screening out clinical drugs that may inhibit the virus, and are rapidly developing vaccines. The emergence of 2019-nCoV reminds us once again of the importance of establishing a systematic coronavirus surveillance network. It also poses new challenges to prevention and control of the emerging epidemic and rapidly responses on scientific research.

Transmission routes of 2019-nCoV and controls in dental practice

A novel ß-coronavirus (2019-nCoV) caused severe and even fetal pneumonia explored in a seafood market of Wuhan city, Hubei province, China, and rapidly spread to other provinces of China and other countries. The 2019-nCoV was different from SARS-CoV, but shared the same host receptor the human angiotensin-converting enzyme 2 (ACE2). The natural host of 2019-nCoV may be the bat Rhinolophus affinis as 2019-nCoV showed 96.2% of whole-genome identity to BatCoV RaTG13. The person-to-person transmission routes of 2019-nCoV included direct transmission, such as cough, sneeze, droplet inhalation transmission, and contact transmission, such as the contact with oral, nasal, and eye mucous membranes. 2019-nCoV can also be transmitted through the saliva, and the fetal-oral routes may also be a potential person-to-person transmission route. The participants in dental practice expose to tremendous risk of 2019-nCoV infection due to the face-to-face communication and the exposure to saliva, blood, and other body fluids, and the handling of sharp instruments. Dental professionals play great roles in preventing the transmission of 2019-nCoV. Here we recommend the infection control measures during dental practice to block the person-to-person transmission routes in dental clinics and hospitals.

2019 novel coronavirus (2019-nCoV) and 2019-nCoV pneumonia/ 2019新型冠状病毒及其感染性肺炎

In the middle of December in 2019, a pneumonia outbreak caused by a new coronavirus, 2019 novel coronavirus (2019-nCoV), emerged in the populations in Wuhan city of China. The epidemic spreads rapidly and has been disseminated throughout the country and to 13 other counties in Asia, Europe, Oceania and North America. To accurately and deeply understand the biological characteristics, epidemiological features and pathogenicity of 2019-nCoV and related immunological characteristics, microbiological examinations and public protection measure, this study reviewed 2019-nCoV and 2019-nCoV pneumonia based on the newest relevant literatures and the newest version of National Diagnosis and Treatment Scheme of 2019-nCoV pneumonia.

Molecular mechanism of evolution and human infection with the novel coronavirus (2019-nCoV)

Since December, 2019, an outbreak of pneumonia caused by the new coronavirus (2019-nCoV) has hit the city of Wuhan in the Hubei Province. With the continuous development of the epidemic, it has become a national public health crisis and calls for urgent antiviral treatments or vaccines. The spike protein on the coronavirus envelope is critical for host cell infection and virus vitality. Previous studies showed that 2019-nCoV is highly homologous to human SARS-CoV and attaches host cells though the binding of the spike receptor binding domain (RBD) domain to the angiotensin-converting enzyme II (ACE2). However, the molecular mechanisms of 2019-nCoV binding to human ACE2 and evolution of 2019-nCoV remain unclear. In this study, we have extensively studied the RBD-ACE2 complex, spike protein, and free RBD systems of 2019-nCoV and SARS-CoV using protein-protein docking and molecular dynamics (MD) simulations. It was shown that the RBD-ACE2 binding free energy for 2019-nCoV is significantly lower than that for SARS-CoV, which is consistent with the fact that 2019-nCoV is much more infectious than SARS-CoV. In addition, the spike protein of 2019-nCoV shows a significantly lower free energy than that of SARS-CoV, suggesting that 2019-nCoV is more stable and able to survive a higher temperature than SARS-CoV. This may also provide insights into the evolution of 2019-nCoV because SARS-like coronaviruses are thought to have originated in bats that are known to have a higher body-temperature than humans. It was also revealed that the RBD of 2019-nCoV is much more flexible especially near the binding site and thus will have a higher entropy penalty upon binding ACE2, compared to the RBD of SARS-CoV. That means that 2019-nCoV will be much more temperature-sensitive in terms of human infection than SARS-CoV. With the rising temperature, 2019-nCoV is expected to decrease its infection ability much faster than SARS-CoV, and get controlled more easily. The present findings are expected to be helpful for the disease prevention and control as well as drug and vaccine development of 2019-nCoV.

SYSTEMATIC REVIEW OF THE ONGOING CLINICAL TRIALS EVALUATING THE DIAGNOSTIC AND THERAPEUTIC INTERVENTIONS TO MANAGE THE RESPIRATORY INFECTION CAUSED BY 2019 NOVEL CORONAVIRUS (2019-NCOV)

TYPE: Abstract Publication TOPIC: Respiratory Care PURPOSE: 2019 novel coronavirus (2019-nCoV) is attributed for outbreak with first human infection detected in December 2019 in Wuhan, China, which has caused clusters of severe respiratory illness like severe acute respiratory syndrome coronavirus. The latest mortality was 2.07%. Currently, the standard care is supportive care, and no treatment is proven to be effective METHODS: We systematically analysed the contemporary protocols of the seven ongoing trials through the Chinese Clinical Trial Registry (4 trials) and the trials registry (3 trials) database. The latest evaluation was on January 29, 2020 with key word ‘2019-nCoV’, for the trials evaluating the diagnostic and the therapeutic interventions to manage the respiratory infection caused by 2019-nCoV RESULTS: Therapeutic interventions include, lopinavir-ritonavir with aerosolized interferon-alpha compared with the adjunctive IV methylprednisolone, umifenovir (broad-spectrum antiviral), SARI-nCoV trial for role of glucocorticoid, three comparative antiviral therapies utilising ribavirin, interferon alpha-1b, lopinavir -ritonavir, Xue-Bi-Jing injection (only Chinese medicine injection approved for sepsis) and novel isothermal nucleic acid amplification technique is under trial for simple, fast and portable diagnosis. The mean number of patients being enrolled is 193 (SD ± 183, maximum 500, minimum 40, range 460, 95% CI 24 to 362). Cumulatively, 1350 patients are targeted across 7 trials. CONCLUSIONS: Varied novel approaches based on the current scientific understanding of the disease are being evaluated for quick and effective management CLINICAL IMPLICATIONS: As the 2019-nCoV becomes a global threat, the rapidity of the Chinese trials for an evidence-based approach are in direction to provide rational, efficacious and potential solutions to effectively manage the disease DISCLOSURE: No significant relationships. KEYWORDS: Ongoing Trials, Systematic Review, 2019-nCoV

2019-nCoV: The Identify-Isolate-Inform (3I) Tool Applied to a Novel Emerging Coronavirus

2019 Novel Coronavirus (2019-nCoV) is an emerging infectious disease closely related to MERS-CoV and SARS-CoV that was first reported in Wuhan City, Hubei Province, China in December 2019. As of January 2020, cases of 2019-nCoV are continuing to be reported in other Eastern Asian countries as well as in the United States, Europe, Australia, and numerous other countries. An unusually high volume of domestic and international travel corresponding to the beginning of the 2020 Chinese New Year complicated initial identification and containment of infected persons. Due to the rapidly rising number of cases and reported deaths, all countries should be considered at risk of imported 2019-nCoV. Therefore, it is essential for prehospital, clinic, and emergency department personnel to be able to rapidly assess 2019-nCoV risk and take immediate actions if indicated. The Identify-Isolate-Inform (3I) Tool, originally conceived for the initial detection and management of Ebola virus and later adjusted for other infectious agents, can be adapted for any emerging infectious disease. This paper reports a modification of the 3I Tool for use in the initial detection and management of patients under investigation for 2019-nCoV. After initial assessment for symptoms and epidemiological risk factors, including travel to affected areas and exposure to confirmed 2019-nCoV patients within 14 days, patients are classified in a risk-stratified system. Upon confirmation of a suspected 2019-nCoV case, affected persons must immediately be placed in airborne infection isolation and the appropriate public health agencies notified. This modified 3I Tool will assist emergency and primary care clinicians, as well as out-of-hospital providers, in effectively managing persons with suspected or confirmed 2019-nCoV.

Pathogenicity and transmissibility of 2019-nCoV—A quick overview and comparison with other emerging viruses

Abstract A zoonotic coronavirus, tentatively labeled as 2019-nCoV by the World Health Organization (WHO), has been identified as the causative agent of the viral pneumonia outbreak in Wuhan, China, at the end of 2019. Although 2019-nCoV can cause a severe respiratory illness like SARS and MERS, evidence from clinics suggested that 2019-nCoV is generally less pathogenic than SARS-CoV, and much less than MERS-CoV. The transmissibility of 2019-nCoV is still debated and needs to be further assessed. To avoid the 2019-nCoV outbreak turning into an epidemic or even a pandemic and to minimize the mortality rate, China activated emergency response procedures, but much remains to be learned about the features of the virus to refine the risk assessment and response. Here, the current knowledge in 2019-nCoV pathogenicity and transmissibility is summarized in comparison with several commonly known emerging viruses, and information urgently needed for a better control of the disease is highlighted.

Remdesivir (GS-5734) as a therapeutic option of 2019-nCOV main protease - in silico approach

2019 - Novel Coronavirus (2019-nCOV), enclosed large genome positive-sense RNA virus characterized by crown-like spikes that protrude from their surface, and have a distinctive replication strategy. The 2019-nCOV belongs to the Coronaviridae family, principally consists of virulent pathogens showing zoonotic property, has emerged as a pandemic outbreak with high mortality and high morbidity rate around the globe and no therapeutic vaccine or drugs against 2019-nCoV are discovered till now. In this study, in silico methods and algorithms were used for sequence, structure analysis and molecular docking on Mpro of 2019-nCOV. The co-crystal structure of 2019-nCOV protease, 6LU7 have â¼99% identity with SARS-CoV protease. The 6LU7 residues, Cys145 and His164 are playing a significant role in replication and are essential for the survival of 2019-nCOV. Alongside, 2019-nCOV Mpro sequence is non-homologous to human host-pathogen. Complete genome sequence analysis, structural and molecular docking results revealed that Remdesivir is having a better binding affinity with -8.2 kcal/mol than the rest of protease inhibitors, and peptide. Remdesivir is strongly forming h-bonds with crucial Mpro residues, Cys145, and His164. Further, MD simulation analysis also confirmed, that these residues are forming H-bond with Remdesivir during 100 ns simulations run and found stable (â¼99%) by RMSD and RMSF. Thus, present in silico study at molecular approaches suggest that, Remdesivir is a potent therapeutic inhibitor against 2019-nCoV.Communicated by Ramaswamy H. Sarma.

Plasma IP-10 and MCP-3 levels are highly associated with disease severity and predict the progression of COVID-19

BACKGROUND: The outbreak of coronavirus disease 2019 (COVID-19) caused by the severe acute respiratory syndrome coronavirus 2 was first reported in Wuhan, December 2019, and continuously poses a serious threat to public health, highlighting the urgent need of identifying biomarkers for disease severity and progression. OBJECTIVE: We sought to identify biomarkers for disease severity and progression of COVID-19. METHODS: Forty-eight cytokines in the plasma samples from 50 COVID-19 cases including 11 critically ill, 25 severe, and 14 moderate patients were measured and analyzed in combination with clinical data. RESULTS: Levels of 14 cytokines were found to be significantly elevated in COVID-19 cases and showed different expression profiles in patients with different disease severity. Moreover, expression levels of IFN-Î³-induced protein 10, monocyte chemotactic protein-3, hepatocyte growth factor, monokine-induced gamma IFN, and macrophage inflammatory protein 1 alpha, which were shown to be highly associated with disease severity during disease progression, were remarkably higher in critically ill patients, followed by severe and then the moderate patients. Serial detection of the 5 cytokines in 16 cases showed that continuously high levels were associated with deteriorated progression of disease and fatal outcome. Furthermore, IFN-Î³-induced protein 10 and monocyte chemotactic protein-3 were excellent predictors for the progression of COVID-19, and the combination of the 2 cytokines showed the biggest area under the curve of the receiver-operating characteristics calculations with a value of 0.99. CONCLUSIONS: In this study, we report biomarkers that are highly associated with disease severity and progression of COVID-19. These findings add to our understanding of the immunopathologic mechanisms of severe acute respiratory syndrome coronavirus 2 infection, and provide potential therapeutic targets and strategies.

Machine intelligence design of 2019-nCoV drugs

Wuhan coronavirus, called 2019-nCoV, is a newly emerged virus that infected more than 9692 people and leads to more than 213 fatalities by January 30, 2020. Currently, there is no effective treatment for this epidemic. However, the viral protease of a coronavirus is well-known to be essential for its replication and thus is an effective drug target. Fortunately, the sequence identity of the 2019-nCoV protease and that of severe-acute respiratory syndrome virus (SARS-CoV) is as high as 96.1%. We show that the protease inhibitor binding sites of 2019-nCoV and SARS-CoV are almost identical, which means all potential anti-SARS-CoV chemotherapies are also potential 2019-nCoV drugs. Here, we report a family of potential 2019-nCoV drugs generated by a machine intelligence-based generative network complex (GNC). The potential effectiveness of treating 2019-nCoV by using some existing HIV drugs is also analyzed.

Advance in human coronaviruses research of host interactions/ 中华实用儿科临床杂志

2019-novel coronavirus (2019-nCoV) is a highly pathogenic human CoV that first emerged in Wuhan in 2019.2019-nCoV has a zoonotic origin and poses a major threat to public health.However, little is known about the viral factors contributing to the high virulence of 2019-nCoV.Many animal viruses, including CoVs, encode proteins that interfere with host gene expression, including those involved in antiviral immune responses, and these viral proteins are often major virulence factors.Human coronaviruses (HCoVs) are known respiratory pathogens associated with a range of respiratory infection.In the past 17 years, the onset of 2019-nCoV, severe acute respiratory syndrome coronavirus (SARS-CoV) and Middle East respiratory syndrome coronavirus (MERS-CoV) have thrust HCoVs into spotlight of the research community due to their high pathogenicity in humans.The recent study of HCoVs-host interactions has contributed extensively to our understanding of infection pathogenesis of 2019-nCoV.This review discuss various host physiopathologic mechanism, such as apoptosis, innate immunity, endoplasmic reticulum (ER) stress response, mitogen-activated protein kinase (MAPK) pathway and nuclear factor kappa B (NF-κB) pathway that may be modulated by HCoVs and provides evidence for the intensive investigate of 2019-nCoV infection.

A novel β-coronavirus (2019-nCoV) caused severe and even fetal pneumonia explored in a seafood market of Wuhan city, Hubei province, China, and rapidly spread to other provinces of China and other countries. The 2019-nCoV was different from SARS-CoV, but shared the same host receptor the human angiotensin-converting enzyme 2 (ACE2). The natural host of 2019-nCoV may be the bat Rhinolophus affinis as 2019-nCoV showed 96.2% of whole-genome identity to BatCoV RaTG13. The person-to-person transmission routes of 2019-nCoV included direct transmission, such as cough, sneeze, droplet inhalation transmission, and contact transmission, such as the contact with oral, nasal, and eye mucous membranes. 2019-nCoV can also be transmitted through the saliva, and the fetal–oral routes may also be a potential person-to-person transmission route. The participants in dental practice expose to tremendous risk of 2019-nCoV infection due to the face-to-face communication and the exposure to saliva, blood, and other body fluids, and the handling of sharp instruments. Dental professionals play great roles in preventing the transmission of 2019-nCoV. Here we recommend the infection control measures during dental practice to block the person-to-person transmission routes in dental clinics and hospitals.

Deep phylogenetic analysis of Orthocoronavirinae genomes traces the origin, evolution and transmission route of 2019 novel coronavirus

The outbreak of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in Wuhan city, China in December 2019 and thereafter its spillover across the world has created a global pandemic and public health crisis. Today, it appears as a threat to human civilization. Scientists and medical practitioners across the world are involved to trace out the origin and evolution of SARS-CoV-2 (also called 2019 novel coronavirus and referred as 2019-nCoV), its transmission route, cause of pathogenicity, and possible remedial action. In this work, we aim to find out the origin, evolutionary patternthat led to its pathogenicity and possible transmission pathway of 2019-nCoV. To achieve the aims we conducted a large-scale deep phylogenetic analysis on the 162 complete Orthocoronavirinae genomes consisting of four genera namely Alphacoronavirus, Betacoronavirus, Deltacoronavirus and Gammacoronavirus, their gene trees analysis and subsequently genome and gene recombination analyses. Our analyses revealed that i) bat, pangolin and anteater are the natural hosts of 2019-nCoV, ii) outbreak of 2019-nCoV took place via inter-intra species transmission mode, iii) host-specific adaptive mutation made 2019-nCoV more virulent, and the presence of widespread recombination events led to the evolution of new 2019-nCoV strain and/or could be determinant of its pathogenicity. Highlights Orthocoronavirinae genome phylogeny revealed that bat, pangolin and anteater are natural reservoir hosts of novel coronavirus (2019-nCoV/SARS-CoV-2). Host-specific adaptive mutation occurred among the coronaviruses. Transmission of 2019-nCoV to human took place by inter-intra species mode of transmission. Presence of widespread recombination events led to the evolution of new 2019-nCoV strain and/or could be determinant of its pathogenicity.

Severe acute respiratory syndrome-related coronavirus: The species and its viruses – a statement of the Coronavirus Study Group

The present outbreak of lower respiratory tract infections, including respiratory distress syndrome, is the third spillover, in only two decades, of an animal coronavirus to humans resulting in a major epidemic. Here, the Coronavirus Study Group (CSG) of the International Committee on Taxonomy of Viruses, which is responsible for developing the official classification of viruses and taxa naming (taxonomy) of the Coronaviridae family, assessed the novelty of the human pathogen tentatively named 2019-nCoV. Based on phylogeny, taxonomy and established practice, the CSG formally recognizes this virus as a sister to severe acute respiratory syndrome coronaviruses (SARS-CoVs) of the species Severe acute respiratory syndrome-related coronavirus and designates it as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). To facilitate communication, the CSG further proposes to use the following naming convention for individual isolates: SARS-CoV-2/Isolate/Host/Date/Location. The spectrum of clinical manifestations associated with SARS-CoV-2 infections in humans remains to be determined. The independent zoonotic transmission of SARS-CoV and SARS-CoV-2 highlights the need for studying the entire (virus) species to complement research focused on individual pathogenic viruses of immediate significance. This research will improve our understanding of virus-host interactions in an ever-changing environment and enhance our preparedness for future outbreaks.

Abstract Background The outbreak of Coronavirus Disease 2019 (COVID-19) caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was first reported in Wuhan, December 2019, and continuously poses a serious threat to public health, highlighting the urgent need of identifying biomarkers for disease severity and progression. Objective To identify biomarkers for disease severity and progression of COVID-19. Methods Forty-eight cytokines in the plasma samples from 50 COVID-19 cases including 11 critically ill, 25 severe and 14 moderate patients were measured and analyzed in combination with clinical data. Results Fourteen cytokines were found to be significantly elevated in COVID-19 cases and showed different expression profiles in patients with different disease severity. Moreover, expression levels of IP-10, MCP-3, HGF, MIG and MIP-1α, which were shown to be highly associated with disease severity during disease progression, were remarkably higher in critically ill patients, followed by severe and then the moderate patients. Serial detection of the five cytokines in 16 cases showed that continuously high levels were associated with deteriorated progression of disease and fatal outcome. Furthermore, IP-10 and MCP-3 were excellent predictors for the progression of COVID-19, and the combination of the two cytokines showed the biggest area under the curve (AUC) of the receiver-operating characteristics (ROC) calculations with a value of 0.99. Conclusion In this study, we report biomarkers that highly associated with disease severity and progression of COVID-19. These findings add to our understanding of the immunopathologic mechanisms of SARS-CoV-2 infection, and provide potential therapeutic targets and strategies.

How far Covid19 virus spread can be curbed byrelaxing lockdown in different stages? -A study inIndian scenario

After the emergence of the first cases in Wuhan, China, the novel coronavirus (2019-nCoV) infection has rapidly spread out to other provinces , neighboring countries and finally has become a global terror. It is indeed a matter of serious concern to study the transmission dynamics of this virus. The potential and severity of an outbreak and providing critical information for identifying the type of disease interventions and intensity can be well understood by the unknown basic reproduction number. A stochastic model can be used to estimate this number with possible safeguard on uncertainties. It is essential to assess how the expensive, resource-intensive measures can contribute to the prevention and control of the 2019-nCoV infection and how long they should be maintained. A short-term forecast of incidences are often of high priority. The challenge is to forecast unseen future simulated data for three different scenarios at some time points. We estimate current levels of transmissibility, over variable time points under different levels of interventions and use that to forecast near-future incidence. The forecasted values of incidence can be used for determining the near future mortality also.

Advance in research of beta coronavirus receptors on ocular surface/ 眼表β属冠状病毒受体的研究进展

2019-Novel coronavirus (2019-nCoV) caused an outbreak of corona virus disease 2019 (COVID-19) from December 2019 in China.2019-nCoV which was identified as a kind of beta coronavirus belongs to one of four coronavirus genera.Except 2019-nCoV, two other beta coronavirus, severe acute respiratory syndrome coronavirus (SARS-CoV) and Middle East respiratory syndrome coronavirus (MERS-CoV) are also quite harmful to human beings.2019-nCoV uses the same cell entry receptor, angiotensin-converting enzyme 2 (ACE2), as SARS-CoV.And dipeptidyl peptidase 4 (DPP4) or CD26 is the cell receptor for MERS-CoV.The expression of ACE2 was found to have obvious positive expression in human corneal and conjunctival epithelium, and corneal endothelium.DPP4 activity was presented in normal animal conjunctival epithelium and fibroblasts of the subjacent connective tissue.It was also presented in the whole corneal epithelium and tear fluid of animal with severe injured corneas.The two receptors, ACE2 and DPP4, are involved in many cellular signaling pathways and pathophysiological processes.Their expression in the cells of ocular surface may be an access route of corona virus in eye, which provides clues to elucidating the pathogenesis of corona virus in the eyeballs.

Pathogenicity and transmissibility of 2019-nCoV-A quick overview and comparison with other emerging viruses

A zoonotic coronavirus, tentatively labeled as 2019-nCoV by the World Health Organization (WHO), has been identified as the causative agent of the viral pneumonia outbreak in Wuhan, China, at the end of 2019. Although 2019-nCoV can cause a severe respiratory illness like SARS and MERS, evidence from clinics suggested that 2019-nCoV is generally less pathogenic than SARS-CoV, and much less than MERS-CoV. The transmissibility of 2019-nCoV is still debated and needs to be further assessed. To avoid the 2019-nCoV outbreak turning into an epidemic or even a pandemic and to minimize the mortality rate, China activated emergency response procedures, but much remains to be learned about the features of the virus to refine the risk assessment and response. Here, the current knowledge in 2019-nCoV pathogenicity and transmissibility is summarized in comparison with several commonly known emerging viruses, and information urgently needed for a better control of the disease is highlighted.

Molecular and serological investigation of 2019-nCoV infected patients: implication of multiple shedding routes

In December 2019, a novel coronavirus (2019-nCoV) caused an outbreak in Wuhan, China, and soon spread to other parts of the world. It was believed that 2019-nCoV was transmitted through respiratory tract and then induced pneumonia, thus molecular diagnosis based on oral swabs was used for confirmation of this disease. Likewise, patient will be released upon two times of negative detection from oral swabs. However, many coronaviruses can also be transmitted through oral-fecal route by infecting intestines. Whether 2019-nCoV infected patients also carry virus in other organs like intestine need to be tested. We conducted investigation on patients in a local hospital who were infected with this virus. We found the presence of 2019-nCoV in anal swabs and blood as well, and more anal swab positives than oral swab positives in a later stage of infection, suggesting shedding and thereby transmitted through oral-fecal route. We also showed serology test can improve detection positive rate thus should be used in future epidemiology. Our report provides a cautionary warning that 2019-nCoV may be shed through multiple routes.

Estimation of the Transmission Risk of the 2019-nCoV and Its Implication for Public Health Interventions

Since the emergence of the first cases in Wuhan, China, the novel coronavirus (2019-nCoV) infection has been quickly spreading out to other provinces and neighboring countries. Estimation of the basic reproduction number by means of mathematical modeling can be helpful for determining the potential and severity of an outbreak and providing critical information for identifying the type of disease interventions and intensity. A deterministic compartmental model was devised based on the clinical progression of the disease, epidemiological status of the individuals, and intervention measures. The estimations based on likelihood and model analysis show that the control reproduction number may be as high as 6.47 (95% CI 5.71–7.23). Sensitivity analyses show that interventions, such as intensive contact tracing followed by quarantine and isolation, can effectively reduce the control reproduction number and transmission risk, with the effect of travel restriction adopted by Wuhan on 2019-nCoV infection in Beijing being almost equivalent to increasing quarantine by a 100 thousand baseline value. It is essential to assess how the expensive, resource-intensive measures implemented by the Chinese authorities can contribute to the prevention and control of the 2019-nCoV infection, and how long they should be maintained. Under the most restrictive measures, the outbreak is expected to peak within two weeks (since 23 January 2020) with a significant low peak value. With travel restriction (no imported exposed individuals to Beijing), the number of infected individuals in seven days will decrease by 91.14% in Beijing, compared with the scenario of no travel restriction.

In December 2019, a novel coronavirus (2019-nCoV) caused an outbreak in Wuhan, China, and soon spread to other parts of the world. It was believed that 2019-nCoV was transmitted through respiratory tract and then induced pneumonia, thus molecular diagnosis based on oral swabs was used for confirmation of this disease. Likewise, patient will be released upon two times of negative detection from oral swabs. However, many coronaviruses can also be transmitted through oral–fecal route by infecting intestines. Whether 2019-nCoV infected patients also carry virus in other organs like intestine need to be tested. We conducted investigation on patients in a local hospital who were infected with this virus. We found the presence of 2019-nCoV in anal swabs and blood as well, and more anal swab positives than oral swab positives in a later stage of infection, suggesting shedding and thereby transmitted through oral–fecal route. We also showed serology test can improve detection positive rate thus should be used in future epidemiology. Our report provides a cautionary warning that 2019-nCoV may be shed through multiple routes.

The novel coronavirus 2019 (2019-nCoV) uses the SARS-coronavirus receptor ACE2 and the cellular protease TMPRSS2 for entry into target cells

The emergence of a novel, highly pathogenic coronavirus, 2019-nCoV, in China, and its rapid national and international spread pose a global health emergency. Coronaviruses use their spike proteins to select and enter target cells and insights into nCoV-2019 spike (S)-driven entry might facilitate assessment of pandemic potential and reveal therapeutic targets. Here, we demonstrate that 2019-nCoV-S uses the SARS-coronavirus receptor, ACE2, for entry and the cellular protease TMPRSS2 for 2019-nCoV-S priming. A TMPRSS2 inhibitor blocked entry and might constitute a treatment option. Finally, we show that the serum form a convalescent SARS patient neutralized 2019-nCoV-S-driven entry. Our results reveal important commonalities between 2019-nCoV and SARS-coronavirus infection, which might translate into similar transmissibility and disease pathogenesis. Moreover, they identify a target for antiviral intervention. One sentence summary The novel 2019 coronavirus and the SARS-coronavirus share central biological properties which can guide risk assessment and intervention.

Genomic characterisation and epidemiology of 2019 novel coronavirus: implications for virus origins and receptor binding

BACKGROUND: In late December, 2019, patients presenting with viral pneumonia due to an unidentified microbial agent were reported in Wuhan, China. A novel coronavirus was subsequently identified as the causative pathogen, provisionally named 2019 novel coronavirus (2019-nCoV). As of Jan 26, 2020, more than 2000 cases of 2019-nCoV infection have been confirmed, most of which involved people living in or visiting Wuhan, and human-to-human transmission has been confirmed. METHODS: We did next-generation sequencing of samples from bronchoalveolar lavage fluid and cultured isolates from nine inpatients, eight of whom had visited the Huanan seafood market in Wuhan. Complete and partial 2019-nCoV genome sequences were obtained from these individuals. Viral contigs were connected using Sanger sequencing to obtain the full-length genomes, with the terminal regions determined by rapid amplification of cDNA ends. Phylogenetic analysis of these 2019-nCoV genomes and those of other coronaviruses was used to determine the evolutionary history of the virus and help infer its likely origin. Homology modelling was done to explore the likely receptor-binding properties of the virus. FINDINGS: The ten genome sequences of 2019-nCoV obtained from the nine patients were extremely similar, exhibiting more than 99·98% sequence identity. Notably, 2019-nCoV was closely related (with 88% identity) to two bat-derived severe acute respiratory syndrome (SARS)-like coronaviruses, bat-SL-CoVZC45 and bat-SL-CoVZXC21, collected in 2018 in Zhoushan, eastern China, but were more distant from SARS-CoV (about 79%) and MERS-CoV (about 50%). Phylogenetic analysis revealed that 2019-nCoV fell within the subgenus Sarbecovirus of the genus Betacoronavirus, with a relatively long branch length to its closest relatives bat-SL-CoVZC45 and bat-SL-CoVZXC21, and was genetically distinct from SARS-CoV. Notably, homology modelling revealed that 2019-nCoV had a similar receptor-binding domain structure to that of SARS-CoV, despite amino acid variation at some key residues. INTERPRETATION: 2019-nCoV is sufficiently divergent from SARS-CoV to be considered a new human-infecting betacoronavirus. Although our phylogenetic analysis suggests that bats might be the original host of this virus, an animal sold at the seafood market in Wuhan might represent an intermediate host facilitating the emergence of the virus in humans. Importantly, structural analysis suggests that 2019-nCoV might be able to bind to the angiotensin-converting enzyme 2 receptor in humans. The future evolution, adaptation, and spread of this virus warrant urgent investigation. FUNDING: National Key Research and Development Program of China, National Major Project for Control and Prevention of Infectious Disease in China, Chinese Academy of Sciences, Shandong First Medical University.

Prediction of numbers of the accumulative confirmed patients (NACP) and the plateau phase of 2019-nCoV in China

In the present study, I propose a novel fitting method to describe the outbreak of 2019-nCoV in China. The fitted data were selected carefully from the non-Hubei part and Hubei Province of China respectively. For the non-Hubei part, the time period of data collection corresponds from the beginning of the policy of isolation to present day. But for Hubei Province, the subjects of Wuhan City and Hubei Province were included from the time of admission to the Huoshenshan Hospital to present day in order to ensure that all or the majority of the confirmed and suspected patients were collected for diagnosis and treatment. The employed basic functions for fitting are the hyperbolic tangent functions [Formula: see text] since in these cases the 2019-nCoV is just an epidemic. Subsequently, the 2019-nCoV will initially expand rapidly and tend to disappear. Therefore, the numbers of the accumulative confirmed patients in different cities, provinces and geographical regions will initially increase rapidly and subsequently stabilize to a plateau phase. The selection of the basic functions for fitting is crucial. In the present study, I found that the hyperbolic tangent functions [Formula: see text] could satisfy the aforementioned properties. By this novel method, I can obtain two significant results. They base on the conditions that the rigorous isolation policy is executed continually. Initially, I can predict the numbers very accurately of the cumulative confirmed patients in different cities, provinces and parts in China, notably, in Wuhan City with the smallest relative error estimated to [Formula: see text] , in Hubei Province with the smallest relative error estimated to [Formula: see text] and in the non-Hubei part of China with the smallest relative error of [Formula: see text] 0.195% in the short-term period of infection. In addition, perhaps I can predict the times when the plateau phases will occur respectively in different regions in the long-term period of infection. Generally for the non-Hubei part of China, the plateau phase of the outbreak of the 2019-nCoV will be expected this March or at the end of this February. In the non-Hubei region of China it is expected that the epidemic will cease on the 30th of March 2020 and following this date no new confirmed patient will be expected. The predictions of the time of Inflection Points and maximum NACP for some important regions may be also obtained. A specific plan for the prevention measures of the 2019-nCoV outbreak must be implemented. This will involve the present returning to work and resuming production in China. Based on the presented results, I suggest that the rigorous isolation policy by the government should be executed regularly during daily life and work duties. Moreover, as many as possible the confirmed and suspected cases should be collected to diagnose or treat.

COVID-19: A Worldwide, Zoonotic, Pandemic Outbreak

Context: An outbreak of a novel, zoonotic coronavirus occurred in December 2019 in the city of Wuhan, China and has now affected almost the entire world, with the maximum confirmed cases being 1 521 252 as of April 10, 2020. The WHO named this coronavirus 2019-nCoV, with COVID-19 being the name for diseases allied with it. Objective: The study intended to examine the features and characteristics of existing human coronaviruses and identify their resemblance to the newly identified 2019-nCoV. Design: The research team performed a literature review, searching relevant literature databases. We searched four databases, PubMed, EMBASE, Web of Science and CNKI (Chinese Database), to identify studies reporting COVID-19. Articles published on or before April 10, 2020 were eligible for inclusion. We used the following search terms: "Coronavirus" or "2019-nCoV" or "COVID-19" or "SARS-CoV" or "MERS-CoV" or "Bat SARS-CoV" or "ACE2 receptor". Setting: This study was take place in School of Pharmacy, Suresh Gyan Vihar University, Jaipur, India. Results: The undistinguishable similarity of the genomic sequences of Severe Respiratory Syndrome (SARS)-CoV, Middle East Respiratory Syndrome (MERS)-CoV, and Bat SARS-CoV-bat-SL-CoVZC45 and bat-SL-CoVZXC21-to nCoV-2019 has facilitated the process of identifying primary treatment measures. Researchers are presuming the existence of angiotensin-converting enzyme 2 (ACE2) receptor binding in nCoV-2019, as in SARS-CoV. Researchers have been examining human-to-human transmission, the possibility of an intermediate host between bats and humans, and the existence of asymptomatic cases. An incubation period of 0 to 14 days has been reported, with acute to chronic symptoms being cough, nasal congestion, high fever, dyspnea, pneumonia, invasive lesions in both lungs, respiratory failure, and even death, including in pediatric cases. Mechanical ventilation, extracorporeal membrane oxygenation, repurposing of antivirals, and plasma infusion have proven to be somewhat effective. Several countries have started clinical trials to evaluate the safety and effectiveness of some drugs, but the ability to vaccinate people with existing or new molecules will require time. Previously learned lessons from SARS and MERS have led some areas to be well equipped in terms of the ability to take speedy action. Conclusions: First-level treatments include repurposing antivirals and antimalarials, and plasma infusion should help, but development of existing or new molecules into vaccines will take time. The unpredictable trajectory of this outbreak demands careful surveillance to monitor the situation, draw strategies, implement control measures, and create proper ethical laws and medical guidelines.

Utilize State Transition Matrix Model to Predict the Novel Corona Virus Infection Peak and Patient Distribution

Background: Since December 2019, a pneumonia caused by the 2019 novel coronavirus (2019-nCoV) has broken out in Wuhan, Hubei province, China. The continuous rising of infected cases has imposed overwhelming pressure on public health decision and medical resource allocation in China. We managed to forecast the infection peak time in Hubei province and the severe and critical case distribution. Methods: We used data resource according to cases reported by the National Health Commission of the People's Republic of China (Jan 25, 2019, to Feb 28, 2020) as the training set to deduce the arrival of the peak infection time and the number of severe and critical cases in Wuhan on subsequent days. Medical observation, discharge, infected, non-Severe, infected and severe, cure and death data were collected and analyzed. Using this state transition matrix model, we will be able predict when the inflection peak time (the maximum open infection cases) in Hubei Province will occur. Also, we can use this model to predict the patient distribution (severe, non-severe) to better allocate medical resource. Under relative pessimistic scenario, the inflection peak time is April 6-April 14. The numbers of critically ill and critically ill patients will lie between 8300-9800 and 2200-2700, respectively. Results: In very optimistic scenarios (daily NCC decay rate of -10%), the peak time of open inflection cases will arrive around February 23-February 26. At the same time, there will be a peak in the numbers of severely ill and critically ill patients, between 6800-7200 and 1800-2000, respectively. In a relative optimistic scenario (daily NCC decay rate of -5%), the inflection case peak time will arrive around February 28-March 2. The numbers of critically ill and critically ill patients will lie between 7100-7800 and 1900-2200, respectively. In a relatively pessimistic scenario (daily NCC decay rate of -1%), the inflection peak time does not arrive around the end of March. Estimated time is April 6-April 14. The numbers of critically ill and critically ill patients will lie between 8300-9800 and 2200-2700, respectively. We are using the diagnosis rate, mortality rate, cure rate as the 2/8 data. There should be room for improvement, if these metrics continue to improve. In that case, the peak time will arrive earlier than our estimation. Also, the severe and critical case ratios are likely to decline as the virus becomes less toxic and medical conditions improve. If that happens, the peak numbers will be lower than predicted above. Conclusion: We can infer that we are still not close to the end of this outbreak and the number of critically ill patients is still climbing. Assisting critical care resources in Hubei province requires the government to consider further tilt, and it is vital to make reasonable management of doctors and medical assistance systems to curb the transmission trend.

Integrative Bioinformatics Analysis Provides Insight into the Molecular Mechanisms of 2019-nCoV

The 2019-nCoV is reported to share the same entry (ACE2) as SARS-CoV according to the updated findings. Analyzing the distribution and expression level of the route of coronavirus may help reveal underlying mechanisms of viral susceptibility and post-infection modulation. In this study, we found that the expression of ACE2 in healthy populations and patients with underlying diseases was not significantly different, suggesting relatively similar susceptibility, which was consistent with current clinical observations. Moreover, based on the expression of ACE2 in smoking individuals, we inferred that long-term smoking might be a risk factor for 2019-nCoV. Analyzing the ACE2 in SARS-CoV infected cells suggested that ACE2 was more than just a receptor but also participated in post-infection regulation, including immune response, cytokine secretion, and viral genome replication. We also constructed Protein-protein interaction (PPI) networks and identified hub genes in viral activity and cytokine secretion. Our findings could explain the clinical symptoms so far and help clinicians and researchers understand the pathogenesis and design therapeutic strategies for 2019-nCoV.

[Detection of 2019-nCoV in the pathological paraffin embedded tissue]

[From SARS to COVID-19: pathogens, receptor, pathogenesis and principles of the treatment].

COVID-19 is an infectious disease caused by 2019-nCoV and characterizes as an atypical pneumonia. Since 2019-nCoV is a newly emerging virus, the pathogenesis of COVID-19 is not well known. Most patients had a self-limited course, and some became severe even death. In this review, the authors compared two coronavirus outbreaks during the past two decades: the SARS-CoV and 2019-nCoV. Among the biological nature of the pathogens, viral receptor distribution on the human cells, and the pathological findings in the targeted organs and clinical features of the patients with the diseases, found similarities and differences between the two diseases. Due to the shared receptor ACE2 and the pathological similarities of the SARS-CoV and 2019-nCoV diseases. They proposed a pathogenesis model for COVID-19. Like the SARS-CoV disease, COVID-19 is a systematic disease and targets the lungs, vasculatures, and the immune system. The basic pathogenesis involves two interlinked processes: a severe lung inflammation and immune deficiency, both of which are related to an inappropriate immune response and over-production of cytokines. Thus, treatment approaches should include antiviral and anti-proinflammatory cytokines, anti-infectious and life support therapies, especially in patients with severe diseases.

Mutations, Recombination and Insertion in the Evolution of 2019-nCoV

The 2019 novel coronavirus (2019-nCoV or SARS-CoV-2) has spread more rapidly than any other betacoronavirus including SARS-CoV and MERS-CoV. However, the mechanisms responsible for infection and molecular evolution of this virus remained unclear. We collected and analyzed 120 genomic sequences of 2019-nCoV including 11 novel genomes from patients in China. Through comprehensive analysis of the available genome sequences of 2019-nCoV strains, we have tracked multiple inheritable SNPs and determined the evolution of 2019-nCoV relative to other coronaviruses. Systematic analysis of 120 genomic sequences of 2019-nCoV revealed co-circulation of two genetic subgroups with distinct SNPs markers, which can be used to trace the 2019-nCoV spreading pathways to different regions and countries. Although 2019-nCoV, human and bat SARS-CoV share high homologous in overall genome structures, they evolved into two distinct groups with different receptor entry specificities through potential recombination in the receptor binding regions. In addition, 2019-nCoV has a unique four amino acid insertion between S1 and S2 domains of the spike protein, which created a potential furin or TMPRSS2 cleavage site. Our studies provided comprehensive insights into the evolution and spread of the 2019-nCoV. Our results provided evidence suggesting that 2019-nCoV may increase its infectivity through the receptor binding domain recombination and a cleavage site insertion. Novel 2019-nCoV sequences revealed the evolution and specificity of betacoronavirus with possible mechanisms of enhanced infectivity.

2019 novel coronavirus (2019-nCoV) outbreak: A new challenge

OBJECTIVES: Following the public-health emergency of international concern (PHEIC) declared by the World Health Organization (WHO) on 30 January 2020 and the recent outbreak caused by 2019 novel coronavirus (2019-nCoV) [officially renamed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)] in China and 29 other countries, we aimed to summarise the clinical aspects of the novelBetacoronavirus disease (COVID-19) and its possible clinical presentations together with suggested therapeutic algorithms for patients who may require antimicrobial treatment. METHODS: The currently available literature was reviewed for microbiologically confirmed infections by 2019-nCoV or COVID-19 at the time of writing (13 February 2020). A literature search was performed using the PubMed database and Cochrane Library. Search terms included 'novel coronavirus' or '2019-nCoV' or 'COVID-19'. RESULTS: Published cases occurred mostly in males (age range, 8-92 years). Cardiovascular, digestive and endocrine system diseases were commonly reported, except previous chronic pulmonary diseases [e.g. chronic obstructive pulmonary disease (COPD), asthma, bronchiectasis] that were surprisingly underreported. Fever was present in all of the case series available, flanked by cough, dyspnoea, myalgia and fatigue. Multiple bilateral lobular and subsegmental areas of consolidation or bilateral ground-glass opacities were the main reported radiological features of 2019-nCoV infection, at least in the early phases of the disease. CONCLUSION: The new 2019-nCoV epidemic is mainly associated with respiratory disease and few extrapulmonary signs. However, there is a low rate of associated pre-existing respiratory co-morbidities.

Cryo-EM Structure of the 2019-nCoV Spike in the Prefusion Conformation

The outbreak of a novel betacoronavirus (2019-nCov) represents a pandemic threat that has been declared a public health emergency of international concern. The CoV spike (S) glycoprotein is a key target for urgently needed vaccines, therapeutic antibodies, and diagnostics. To facilitate medical countermeasure (MCM) development we determined a 3.5 Å-resolution cryo-EM structure of the 2019-nCoV S trimer in the prefusion conformation. The predominant state of the trimer has one of the three receptor-binding domains (RBDs) rotated up in a receptor-accessible conformation. We also show biophysical and structural evidence that the 2019-nCoV S binds ACE2 with higher affinity than SARS-CoV S. Additionally we tested several published SARS-CoV RBD-specific monoclonal antibodies and found that they do not have appreciable binding to nCoV-2019 S, suggesting antibody cross-reactivity may be limited between the two virus RBDs. The atomic-resolution structure of 2019-nCoV S should enable rapid development and evaluation of MCMs to address the ongoing public health crisis.

2019-nCoV: new challenges from coronavirus

The outbreak of pneumonia caused by the novel coronavirus 2019-nCoV in Wuhan, Hubei province of China, at the end of 2019 shaped tremendous challenges to China's public health and clinical treatment The virus belongs to the βgenus Coronavirus in the family Corornaviridae, and is closely related to SARS-CoV and MERS-CoV, causing severe symptoms of pneumonia The virus is transmitted through droplets, close contact, and other means, and patients in the incubation period could potentially transmit the virus to other persons According to current observations, 2019-nCoV is weaker than SARS in pathogenesis, but has stronger transmission competence;it's mechanism of cross-species spread might be related with angiotensin-converting enzyme Ⅱ(ACE2), which is consistent with the receptor SARS-CoV After the outbreak of this disease, Chinese scientists invested a lot of energy to carry out research by developing rapid diagnostic reagents, identifying the characters of the pathogen, screening out clinical drugs that may inhibit the virus, and are rapidly developing vaccines The emergence of 2019-nCoV reminds us once again of the importance of establishing a systematic coronavirus surveillance network It also poses new challenges to prevention and control of the emerging epidemic and rapidly responses on scientific research

Genomic characterization of the 2019 novel human-pathogenic coronavirus isolated from a patient with atypical pneumonia after visiting Wuhan

A mysterious outbreak of atypical pneumonia in late 2019 was traced to a seafood wholesale market in Wuhan of China Within a few weeks, a novel coronavirus tentatively named as 2019 novel coronavirus (2019-nCoV) was announced by the World Health Organization We performed bioinformatics analysis on a virus genome from a patient with 2019-nCoV infection and compared it with other related coronavirus genomes Overall, the genome of 2019-nCoV has 89% nucleotide identity with bat SARS-like-CoVZXC21 and 82% with that of human SARS-CoV The phylogenetic trees of their orf1a/b, Spike, Envelope, Membrane and Nucleoprotein also clustered closely with those of the bat, civet and human SARS coronaviruses However, the external subdomain of Spike's receptor binding domain of 2019-nCoV shares only 40% amino acid identity with other SARS-related coronaviruses Remarkably, its orf3b encodes a completely novel short protein Furthermore, its new orf8 likely encodes a secreted protein with an alpha-helix, following with a beta-sheet(s) containing six strands Learning from the roles of civet in SARS and camel in MERS, hunting for the animal source of 2019-nCoV and its more ancestral virus would be important for understanding the origin and evolution of this novel lineage B betacoronavirus These findings provide the basis for starting further studies on the pathogenesis, and optimizing the design of diagnostic, antiviral and vaccination strategies for this emerging infection FAU - Chan, Jasper Fuk-Woo

COVID-19: A Worldwide, Zoonotic, Pandemic Outbreak.

Context An outbreak of a novel, zoonotic coronavirus occurred in December 2019 in the city of Wuhan, China and has now affected almost the entire world, with the maximum confirmed cases being 1 521 252 as of April 10, 2020. The WHO named this coronavirus 2019-nCoV, with COVID-19 being the name for diseases allied with it. Objective The study intended to examine the features and characteristics of existing human coronaviruses and identify their resemblance to the newly identified 2019-nCoV. Design The research team performed a literature review, searching relevant literature databases. We searched four databases, PubMed, EMBASE, Web of Science and CNKI (Chinese Database), to identify studies reporting COVID-19. Articles published on or before April 10, 2020 were eligible for inclusion. We used the following search terms: "Coronavirus" or "2019-nCoV" or "COVID-19" or "SARS-CoV" or "MERS-CoV" or "Bat SARS-CoV" or "ACE2 receptor". Setting This study was take place in School of Pharmacy, Suresh Gyan Vihar University, Jaipur, India. Results The undistinguishable similarity of the genomic sequences of Severe Respiratory Syndrome (SARS)-CoV, Middle East Respiratory Syndrome (MERS)-CoV, and Bat SARS-CoV-bat-SL-CoVZC45 and bat-SL-CoVZXC21-to nCoV-2019 has facilitated the process of identifying primary treatment measures. Researchers are presuming the existence of angiotensin-converting enzyme 2 (ACE2) receptor binding in nCoV-2019, as in SARS-CoV. Researchers have been examining human-to-human transmission, the possibility of an intermediate host between bats and humans, and the existence of asymptomatic cases. An incubation period of 0 to 14 days has been reported, with acute to chronic symptoms being cough, nasal congestion, high fever, dyspnea, pneumonia, invasive lesions in both lungs, respiratory failure, and even death, including in pediatric cases. Mechanical ventilation, extracorporeal membrane oxygenation, repurposing of antivirals, and plasma infusion have proven to be somewhat effective. Several countries have started clinical trials to evaluate the safety and effectiveness of some drugs, but the ability to vaccinate people with existing or new molecules will require time. Previously learned lessons from SARS and MERS have led some areas to be well equipped in terms of the ability to take speedy action. Conclusions First-level treatments include repurposing antivirals and antimalarials, and plasma infusion should help, but development of existing or new molecules into vaccines will take time. The unpredictable trajectory of this outbreak demands careful surveillance to monitor the situation, draw strategies, implement control measures, and create proper ethical laws and medical guidelines.

The emergence of novel-coronavirus and its replication cycle - An overview

Recently, a new viral-based infection has emerged as a respiratory disease caused by a novel (new) coronavirus that was first detected in Wuhan City, China. With any or many reasons, this newly emerged novel-Coronavirus (2019-nCoV) has now been recognized in more than 70 locations around the globe. The disease caused by 2019-nCoV has been named as “coronavirus disease 2019 - COVID-19”. Due to the rising number of confirmed 2019-nCoV infected cases and widespread detection, the World Health Organization (WHO) has announced 2019-nCoV as a threatening health concern, and urgent robust actions are of supreme interest to tackle this global health emergency. Owing to this new emergence, we know relatively little about 2019-nCoV, which is a highly pathogenic human pathogen. To completely overcome this life-threatening 2019-nCoV pathogen, further in-depth studies are needed to gain insight and complete understanding about its fast mode spread, replication, and pathogenesis. Since the first appearance and detection of 2019-nCoV and COVID-19, respectively, the current literature lacks the global perspective and replication cycle of 2019-nCoV. Thus, herein, an effort has been made to cover this literature gap. A proper understanding of the 2019-nCoV replication will further insight and strengthen the infection control measures, transmission prevention, and vaccine development, effectively.

Effectiveness of glucocorticoid therapy in patients with severe coronavirus disease 2019: protocol of a randomized controlled trial

BACKGROUND: At the end of 2019, a novel coronavirus outbreak emerged in Wuhan, China, and its causative organism has been subsequently designated the 2019 novel coronavirus (2019-nCoV). The effectiveness of adjunctive glucocorticoid therapy in the management of 2019-nCoV-infected patients with severe lower respiratory tract infections is not clear, and warrants further investigation. METHODS: The present study will be conducted as an open-labeled, randomized, controlled trial. We will enrol 48 subjects from Chongqing Public Health Medical Center. Each eligible subject will be assigned to an intervention group (methylprednisolone via intravenous injection at a dose of 1–2 mg/kg/day for 3 days) or a control group (no glucocorticoid use) randomly, at a 1:1 ratio. Subjects in both groups will be invited for 28 days of follow-up which will be scheduled at four consecutive visit points. We will use the clinical improvement rate as our primary endpoint. Secondary endpoints include the timing of clinical improvement after intervention, duration of mechanical ventilation, duration of hospitalization, overall incidence of adverse events, as well as rate of adverse events at each visit, and mortality at 2 and 4 weeks. DISCUSSION: The present coronavirus outbreak is the third serious global coronavirus outbreak in the past two decades. Oral and parenteral glucocorticoids have been used in the management of severe respiratory symptoms in coronavirus-infected patients in the past. However, there remains no definitive evidence in the literature for or against the utilization of systemic glucocorticoids in seriously ill patients with coronavirus-related severe respiratory disease, or indeed in other types of severe respiratory disease. In this study, we hope to discover evidence either supporting or opposing the systemic therapeutic administration of glucocorticoids in patients with severe coronavirus disease 2019. TRIAL REGISTRATION: ClinicalTrials.gov, ChiCTR2000029386, http://www.chictr.org.cn/showproj.aspx?proj=48777.

Transmission of 2019-nCoV Infection from an Asymptomatic Contact in Germany

Protein Structure and Sequence Reanalysis of 2019-nCoV Genome Refutes Snakes as Its Intermediate Host and the Unique Similarity between Its Spike Protein Insertions and HIV-1

[Image: see text] As the infection of 2019-nCoV coronavirus is quickly developing into a global pneumonia epidemic, the careful analysis of its transmission and cellular mechanisms is sorely needed. In this Communication, we first analyzed two recent studies that concluded that snakes are the intermediate hosts of 2019-nCoV and that the 2019-nCoV spike protein insertions share a unique similarity to HIV-1. However, the reimplementation of the analyses, built on larger scale data sets using state-of-the-art bioinformatics methods and databases, presents clear evidence that rebuts these conclusions. Next, using metagenomic samples from Manis javanica, we assembled a draft genome of the 2019-nCoV-like coronavirus, which shows 73% coverage and 91% sequence identity to the 2019-nCoV genome. In particular, the alignments of the spike surface glycoprotein receptor binding domain revealed four times more variations in the bat coronavirus RaTG13 than in the Manis coronavirus compared with 2019-nCoV, suggesting the pangolin as a missing link in the transmission of 2019-nCoV from bats to human.

BACKGROUND: At the end of 2019, a novel coronavirus outbreak causative organism has been subsequently designated the 2019 novel coronavirus (2019-nCoV). The effectiveness of adjunctive glucocorticoid therapy in the management of 2019-nCoV-infected patients with severe lower respiratory tract infections is not clear, and warrants further investigation. METHODS: The present study will be conducted as an open-labeled, randomized, controlled trial. We will enrol 48 subjects from Chongqing Public Health Medical Center. Each eligible subject will be assigned to an intervention group (methylprednisolone via intravenous injection at a dose of 1-2 mg/kg/day for 3 days) or a control group (no glucocorticoid use) randomly, at a 1:1 ratio. Subjects in both groups will be invited for 28 days of follow-up which will be scheduled at four consecutive visit points. We will use the clinical improvement rate as our primary endpoint. Secondary endpoints include the timing of clinical improvement after intervention, duration of mechanical ventilation, duration of hospitalization, overall incidence of adverse events, as well as rate of adverse events at each visit, and mortality at 2 and 4 weeks. DISCUSSION: The present coronavirus outbreak is the third serious global coronavirus outbreak in the past two decades. Oral and parenteral glucocorticoids have been used in the management of severe respiratory symptoms in coronavirus-infected patients in the past. However, there remains no definitive evidence in the literature for or against the utilization of systemic glucocorticoids in seriously ill patients with coronavirus-related severe respiratory disease, or indeed in other types of severe respiratory disease. In this study, we hope to discover evidence either supporting or opposing the systemic therapeutic administration of glucocorticoids in patients with severe coronavirus disease 2019. TRIAL REGISTRATION: ClinicalTrials.gov, ChiCTR2000029386, http://www.chictr.org.cn/showproj.aspx?proj=48777.

Estimating the Unreported Number of Novel Coronavirus (2019-nCoV) Cases in China in the First Half of January 2020: A Data-Driven Modelling Analysis of the Early Outbreak

Background: In December 2019, an outbreak of respiratory illness caused by a novel coronavirus (2019-nCoV) emerged in Wuhan, China and has swiftly spread to other parts of China and a number of foreign countries. The 2019-nCoV cases might have been under-reported roughly from 1 to 15 January 2020, and thus we estimated the number of unreported cases and the basic reproduction number, R(0), of 2019-nCoV. Methods: We modelled the epidemic curve of 2019-nCoV cases, in mainland China from 1 December 2019 to 24 January 2020 through the exponential growth. The number of unreported cases was determined by the maximum likelihood estimation. We used the serial intervals (SI) of infection caused by two other well-known coronaviruses (CoV), Severe Acute Respiratory Syndrome (SARS) and Middle East Respiratory Syndrome (MERS) CoVs, as approximations of the unknown SI for 2019-nCoV to estimate R(0). Results: We confirmed that the initial growth phase followed an exponential growth pattern. The under-reporting was likely to have resulted in 469 (95% CI: 403–540) unreported cases from 1 to 15 January 2020. The reporting rate after 17 January 2020 was likely to have increased 21-fold (95% CI: 18–25) in comparison to the situation from 1 to 17 January 2020 on average. We estimated the R(0) of 2019-nCoV at 2.56 (95% CI: 2.49–2.63). Conclusion: The under-reporting was likely to have occurred during the first half of January 2020 and should be considered in future investigation.

Overcoming Barriers: The Endothelium As a Linchpin of Coronavirus Disease 2019 Pathogenesis?

OBJECTIVE Coronavirus disease 2019 (COVID-19) is a global pandemic involving >5 500 000 cases worldwide as of May 26, 2020. The culprit is the severe acute respiratory syndrome coronavirus-2, which invades cells by binding to angiotensin-converting enzyme 2. While the majority of patients mount an appropriate antiviral response and recover at home, others progress to respiratory distress requiring hospital admission for supplemental oxygen. In severe cases, deterioration to acute respiratory distress syndrome necessitating mechanical ventilation, development of severe thrombotic events, or cardiac injury and dysfunction occurs. In this review, we highlight what is known to date about coronavirus disease 2019 and cardiovascular risk, focusing in on the putative role of the endothelium in disease susceptibility and pathogenesis. Approach and Results: Cytokine-driven vascular leak in the lung alveolar-endothelial interface facilitates acute lung injury in the setting of viral infection. Given that the virus affects multiple organs, including the heart, it likely gains access into systemic circulation by infecting or passing from the respiratory epithelium to the endothelium for viral dissemination. Indeed, cardiovascular complications of coronavirus disease 2019 are highly prevalent and include acute cardiac injury, myocarditis, and a hypercoagulable state, all of which may be influenced by altered endothelial function. Notably, the disease course is worse in individuals with preexisting comorbidities that involve endothelial dysfunction and may be linked to elevated ACE2 (angiotensin-converting enzyme 2) expression, such as diabetes mellitus, hypertension, and cardiovascular disease. CONCLUSIONS Rapidly emerging data on coronavirus disease 2019, together with results from studies on severe acute respiratory syndrome coronavirus-1, are providing insight into how endothelial dysfunction may contribute to the pandemic that is paralyzing the globe. This may, in turn, inform the design of biomarkers predictive of disease course, as well as therapeutics targeting pathogenic endothelial responses.

Role of the Eye in Transmitting Human Coronavirus: What We Know and What We Do Not Know

The outbreak of the current 2019 novel coronavirus (2019-nCoV, now named SARS-CoV-2) infection has become a worldwide health threat. Currently, more information is needed so as to further understand the transmission and clinical characteristics of 2019-nCoV infection and the infection control procedures required. Recently, the role of the eye in transmitting 2019-nCoV has been intensively discussed. Previous investigations of other highly infectious human CoVs, that is, severe acute respiratory syndrome coronavirus (SARS-CoV) and the Middle East respiratory syndrome coronavirus (MERS-CoV), may provide useful information. In this review, we describe the genomics and morphology of human CoVs, the epidemiology, systemic and ophthalmic manifestations, and mechanisms of human CoV infection, and recommendations for infection control procedures. The role of the eye in the transmission of 2019-nCoV is discussed in detail. Although the conjunctiva is directly exposed to extraocular pathogens, and the mucosa of the ocular surface and upper respiratory tract are connected by the nasolacrimal duct and share the same entry receptors for some respiratory viruses, the eye is rarely involved in human CoV infection, conjunctivitis is quite rare in patients with 2019-nCoV infection, and the CoV RNA positive rate by RT-PCR test in tears and conjunctival secretions from patients with 2019-nCoV and SARS-CoV infection is also extremely low. This suggests that the eye is neither a preferred organ of human CoV infection nor a preferred gateway of entry for human CoVs for infecting the respiratory tract. However, pathogens that the ocular surface is exposed to might be transported to nasal and nasopharyngeal mucosa by constant tear rinsing through the lacrimal duct system and then cause respiratory tract infection. Considering that close doctor-patient contact is quite common in ophthalmic practice and is apt to transmit human CoVs by droplets and fomites, strict hand hygiene and proper personal protection are highly recommended for health care workers to avoid hospital-related viral transmission during ophthalmic practice.

Moral imperative for the immediate release of 2019-nCoV sequence data

Phylogenetic study of 2019-nCoV by using alignment-free method

The origin and early spread of 2019-nCoV is studied by phylogenetic analysis using IC-PIC alignment-free method based on DNA/RNA sequence information correlation (IC) and partial information correlation (PIC). The topology of phylogenetic tree of Betacoronavirus is remarkably consistent with biologist's systematics, classifies 2019-nCoV as Sarbecovirus of Betacoronavirus and supports the assumption that these novel viruses are of bat origin with pangolin as one of the possible intermediate hosts. The novel virus branch of phylogenetic tree shows location-virus linkage. The placement of root of the early 2019-nCoV tree is studied carefully in Neighbor Joining consensus algorithm by introducing different out-groups (Bat-related coronaviruses, Pangolin coronaviruses and HIV viruses etc.) and comparing with UPGMA consensus trees. Several oldest branches (lineages) of the 2019-nCoV tree are deduced that means the COVID-19 may begin to spread in several regions in the world before its outbreak in Wuhan.

Specific ACE2 expression in small intestinal enterocytes may cause gastrointestinal symptoms and injury after 2019-nCoV infection

The coronavirus disease 2019 (COVID-19) was first reported in Wuhan, China and rapidly spread in other countries in December 2019. The infected patients presented with fever, respiratory symptoms, sometimes with digestive and other systemic manifestations, and some progressed with a severe acute respiratory syndrome or even death. Associated digestive symptoms were frequently observed in the patients, with an unknown significance and mechanism. ACE2, as the major known functional receptor of the 2019 novel coronavirus (2019-nCoV) attracted our attention. We collected the clinical data of the 2019-nCoV-infected patients from published studies and extracted the data about the incidence of gastrointestinal symptoms. Furthermore, we used online datasets to analyze ACE2 expression in different human organs, especially in the small intestine, to explore the relationship between ACE2 expression patterns and clinical symptoms. We found that diarrhea accounted for a notable proportion of COVID-19 patients, ranging from 8.0% to 12.9%. The results reveal that ACE2 mRNA and protein are highly expressed in the small intestinal enterocytes but not in the goblet cells or intestinal immune cells. High expression of ACE2 on the surface cells in the digestive tract may lead to gastrointestinal symptoms and inflammation susceptibility. Overall, digestive symptoms were common in the COVID-19 patients. ACE2 expression on surface cells of the small intestine may mediate the invasion and amplification of the virus and activation of gastrointestinal inflammation. It is a possible mechanism of digestive symptoms in the COVID-19 patients and explains the presence of the virus in patients' stool samples. The study also highlights the necessity of taking stool samples for suspected patients to help in early diagnosis and assessment of disease status.

Medical Journals and the 2019-nCoV Outbreak.

Deep Learning Based Drug Screening for Novel Coronavirus 2019-nCov

A novel coronavirus, called 2019-nCoV, was recently found in Wuhan, Hubei Province of China, and now is spreading across China and other parts of the world. Although there are some drugs to treat 2019-nCoV, there is no proper scientific evidence about its activity on the virus. It is of high significance to develop a drug that can combat the virus effectively to save valuable human lives. It usually takes a much longer time to develop a drug using traditional methods. For 2019-nCoV, it is now better to rely on some alternative methods such as deep learning to develop drugs that can combat such a disease effectively since 2019-nCoV is highly homologous to SARS-CoV. In the present work, we first collected virus RNA sequences of 18 patients reported to have 2019-nCoV from the public domain database, translated the RNA into protein sequences, and performed multiple sequence alignment. After a careful literature survey and sequence analysis, 3C-like protease is considered to be a major therapeutic target and we built a protein 3D model of 3C-like protease using homology modeling. Relying on the structural model, we used a pipeline to perform large scale virtual screening by using a deep learning based method to accurately rank/identify protein–ligand interacting pairs developed recently in our group. Our model identified potential drugs for 2019-nCoV 3C-like protease by performing drug screening against four chemical compound databases (Chimdiv, Targetmol-Approved_Drug_Library, Targetmol-Natural_Compound_Library, and Targetmol-Bioactive_Compound_Library) and a database of tripeptides. Through this paper, we provided the list of possible chemical ligands (Meglumine, Vidarabine, Adenosine, d-Sorbitol, d-Mannitol, Sodium_gluconate, Ganciclovir and Chlorobutanol) and peptide drugs (combination of isoleucine, lysine and proline) from the databases to guide the experimental scientists and validate the molecules which can combat the virus in a shorter time. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s12539-020-00376-6) contains supplementary material, which is available to authorized users.

High-throughput sequencing for confirmation of suspected 2019-nCoV infection identified by fluorescence quantitative polymerase chain reaction

Consensus on emergency surgery and infection prevention and control for severe trauma patients with 2019 novel coronavirus pneumonia/ 中华创伤杂志

A novel coronavirus pneumonia (NCP) epidemic has occurred in Wuhan, Hubei Province since December 2019, caused by a novel coronavirus (2019-nCoV) never been seen previously in human. China has imposed the strictest quarantine and closed management measures in history to control the spreading of the disease. However, severe trauma can still occur in the NCP patients. In order to standardize the emergency treatment and the infection prevention and control of severe trauma patients with hidden infection, suspected or confirmed infection of 2019-nCoV, Trauma Surgery Branch of Chinese Medical Doctors' Association organized this expert consensus. The consensus illustrated the classification of the NCP patients, severe trauma patients in need of emergency surgery, emergency surgery type, hierarchical protection for medical personnel and treatment places. Meanwhile, the consensus standardized the screening, injury severity evaluation, emergency surgical treatment strategy and postoperative management strategy of severe trauma patients during the epidemic period of NCP, providing a basis for the clinical treatment of such kind of patients.

A rapid advice guideline for the diagnosis and treatment of 2019 novel coronavirus (2019-nCoV) infected pneumonia (standard version)

In December 2019, a new type viral pneumonia cases occurred in Wuhan, Hubei Province; and then named "2019 novel coronavirus (2019-nCoV)" by the World Health Organization (WHO) on 12 January 2020. For it is a never been experienced respiratory disease before and with infection ability widely and quickly, it attracted the world's attention but without treatment and control manual. For the request from frontline clinicians and public health professionals of 2019-nCoV infected pneumonia management, an evidence-based guideline urgently needs to be developed. Therefore, we drafted this guideline according to the rapid advice guidelines methodology and general rules of WHO guideline development; we also added the first-hand management data of Zhongnan Hospital of Wuhan University. This guideline includes the guideline methodology, epidemiological characteristics, disease screening and population prevention, diagnosis, treatment and control (including traditional Chinese Medicine), nosocomial infection prevention and control, and disease nursing of the 2019-nCoV. Moreover, we also provide a whole process of a successful treatment case of the severe 2019-nCoV infected pneumonia and experience and lessons of hospital rescue for 2019-nCoV infections. This rapid advice guideline is suitable for the first frontline doctors and nurses, managers of hospitals and healthcare sections, community residents, public health persons, relevant researchers, and all person who are interested in the 2019-nCoV.

Advance in research of beta coronavirus receptors on ocular surface/ 中华实验眼科杂志

Novel coronavirus (2019-nCoV) caused an outbreak of corona virus disease 2019 (COVID-19) from December 2019 in China. 2019-nCoV which was identified is a kind of beta coronavirus belongs to one of four coronavirus genera. Except 2019-nCoV, two other beta coronavirus, severe acute respiratory syndrome coronavirus (SARS-CoV) and Middle East respiratory syndrome coronavirus (MERS-CoV) are also quite harmful to human beings. 2019-nCoV uses the same cell entry receptor, angiotensin-converting enzyme 2 (ACE2), as SARS-CoV. And dipeptidyl peptidase 4 (DPP4) or CD26 is the cell receptor for MERS-CoV. The expression of ACE2 was found to have obvious positive expression in human corneal and conjunctival epithelium, and corneal endothelium. DPP4 activity was presented in normal animal conjunctival epithelium and fibroblasts of the subjacent connective tissue. It was also presented in the whole corneal epithelium and tear fluid of animal with severe injured corneas. The two receptors, ACE2 and DPP4, involve in many cellular signaling pathways and pathophysiological processes. Their expression in the cells of ocular surface may be an access route of corona virus in eye, which provides clues to elucidating the pathogenesis of corona virus in the eyeballs.

Specific ACE2 Expression in Cholangiocytes May Cause Liver Damage After 2019-nCoV Infection

A newly identified coronavirus, 2019-nCoV, has been posing significant threats to public health since December 2019. ACE2, the host cell receptor for severe acute respiratory syndrome coronavirus (SARS), has recently been demonstrated in mediating 2019-nCoV infection. Interestingly, besides the respiratory system, substantial proportion of SARS and 2019-nCoV patients showed signs of various degrees of liver damage, the mechanism and implication of which have not yet been determined. Here, we performed an unbiased evaluation of cell type specific expression of ACE2 in healthy liver tissues using single cell RNA-seq data of two independent cohorts, and identified specific expression in cholangiocytes. The results indicated that virus might directly bind to ACE2 positive cholangiocytes but not necessarily hepatocytes. This finding suggested the liver abnormalities of SARS and 2019-nCoV patients may not be due to hepatocyte damage, but cholangiocyte dysfunction and other causes such as drug induced and systemic inflammatory response induced liver injury. Our findings indicate that special care of liver dysfunction should be installed in treating 2019-nCoV patients during the hospitalization and shortly after cure.

Does infection of 2019 novel coronavirus cause acute and/or chronic sialadenitis?

2019 novel coronavirus (2019-nCoV) is widespread in China and other countries. The target of 2019-nCoV and severe acute respiratory syndrome coronavirus (SARS-CoV) is angiotensin-converting enzyme 2 (ACE2) positive cells. ACE2 is present in the salivary gland duct epithelium, and thus it could be the target of 2019-nCoV and SARS-CoV. SARS-CoV-related animal model experiments show that it can infect the epithelial cells on the salivary gland duct in Chinese rhesus macaques by targeting ACE2. Clinical studies confirmed that 2019-nCoV and SARS-CoV could be detected in saliva of human patients. We hypothesize that the infection of 2019-nCoV and SARS-CoV will lead to inflammatory pathological lesions in patients' target organs, and possibly inflammatory lesions in salivary glands. 2019-nCoV may cause acute sialoadenitis in the acute phase of infection. After the acute phase, chronic sialoadenitis may be caused by fibrosis repairment. Although there was no direct evidence to prove this, the available indirect evidence indicates a high probability of our hypothesis.

[From SARS to COVID-19: pathogens, receptor, pathogenesis and principles of the treatment]

COVID-19 is an infectious disease caused by 2019-nCoV and characterizes as an atypical pneumonia. Since 2019-nCoV is a newly emerging virus, the pathogenesis of COVID-19 is not well known. Most patients had a self-limited course, and some became severe even death. In this review, the authors compared two coronavirus outbreaks during the past two decades: the SARS-CoV and 2019-nCoV. Among the biological nature of the pathogens, viral receptor distribution on the human cells, and the pathological findings in the targeted organs and clinical features of the patients with the diseases, found similarities and differences between the two diseases had been found. Due to the shared receptor ACE2 and the pathological similarities of the SARS-CoV and 2019-nCoV diseases,authors proposed a pathogenesis model for COVID-19. Like the SARS-CoV disease, COVID-19 is a systematic disease and targets the lungs, vasculatures, and the immune system. The basic pathogenesis involves two interlinked processes: a severe lung inflammation and immune deficiency, both of which were related to an inappropriate immune response and over-production of cytokines. Thus, treatment approaches should include antiviral and anti-proinflammatory cytokines, anti-infectious and life support therapies, especially in patients with severe diseases.

Genomic characterization of the 2019 novel human-pathogenic coronavirus isolated from a patient with atypical pneumonia after visiting Wuhan

A mysterious outbreak of atypical pneumonia in late 2019 was traced to a seafood wholesale market in Wuhan of China. Within a few weeks, a novel coronavirus tentatively named as 2019 novel coronavirus (2019-nCoV) was announced by the World Health Organization. We performed bioinformatics analysis on a virus genome from a patient with 2019-nCoV infection and compared it with other related coronavirus genomes. Overall, the genome of 2019-nCoV has 89% nucleotide identity with bat SARS-like-CoVZXC21 and 82% with that of human SARS-CoV. The phylogenetic trees of their orf1a/b, Spike, Envelope, Membrane and Nucleoprotein also clustered closely with those of the bat, civet and human SARS coronaviruses. However, the external subdomain of Spike’s receptor binding domain of 2019-nCoV shares only 40% amino acid identity with other SARS-related coronaviruses. Remarkably, its orf3b encodes a completely novel short protein. Furthermore, its new orf8 likely encodes a secreted protein with an alpha-helix, following with a beta-sheet(s) containing six strands. Learning from the roles of civet in SARS and camel in MERS, hunting for the animal source of 2019-nCoV and its more ancestral virus would be important for understanding the origin and evolution of this novel lineage B betacoronavirus. These findings provide the basis for starting further studies on the pathogenesis, and optimizing the design of diagnostic, antiviral and vaccination strategies for this emerging infection.

COVID-2019: update on epidemiology, disease spread and management

With each passing day, more cases of Coronavirus disease (COVID-2019) are being detected and unfortunately the fear of novel corona virus 2019 (2019-nCoV) becoming a pandemic disease has come true. Constant efforts at individual, national, and international level are being made in order to understand the genomics, hosts, modes of transmission and epidemiological link of nCoV-2019. As of now, whole genome sequence of the newly discovered coronavirus has already been decoded. Genomic characterization nCoV-2019 have shown close homology with bat-derived severe acute respiratory syndrome (SARS)-like coronaviruses, bat-SL-CoVZC45 and bat-SL-CoVZXC21. Structural analysis of the receptor binding site has confirmed that 2019-nCoV binds with the same ACE 2 receptor protein as human SARS virus. Compared to the previous coronavirus outbreaks, the overall mortality rate is relatively low for COVID-2019 (2-3%). Suspected cases must be quarantined till their test comes positive or they clear infection. At present, treatment of COVID-2019 is mostly based on the knowledge gained from the SARS and MERS outbreaks. Remdesivir, originally develop as a treatment for Ebola virus disease and Marburg virus infections, is being studied for it effectiveness against 2019-nCoV infection. Many other antiviral agents and vaccines are being tested but most of them are in phase I or II and hence unlikely to be of any benefit immediately with regards to current outbreak. Hence, the standard infection control techniques and preventive steps for healthy individuals and supportive care for the confirmed cases is the best available strategy to deal with current viral outbreak. .

Isolation and Characterization of 2019-nCoV-like Coronavirus from Malayan Pangolins

The outbreak of 2019-nCoV in the central Chinese city of Wuhan at the end of 2019 poses unprecedent public health challenges to both China and the rest world1. The new coronavirus shares high sequence identity to SARS-CoV and a newly identified bat coronavirus2. While bats may be the reservoir host for various coronaviruses, whether 2019-nCoV has other hosts is still ambiguous. In this study, one coronavirus isolated from Malayan pangolins showed 100%, 98.2%, 96.7% and 90.4% amino acid identity with 2019-nCoV in the E, M, N and S genes, respectively. In particular, the receptor-binding domain of the S protein of the Pangolin-CoV is virtually identical to that of 2019-nCoV, with one amino acid difference. Comparison of available genomes suggests 2019-nCoV might have originated from the recombination of a Pangolin-CoV-like virus with a Bat-CoV-RaTG13-like virus. Infected pangolins showed clinical signs and histopathological changes, and the circulating antibodies reacted with the S protein of 2019-nCoV. The isolation of a coronavirus that is highly related to 2019-nCoV in the pangolins suggests that these animals have the potential to act as the intermediate host of 2019-nCoV. The newly identified coronavirus in the most-trafficked mammal could represent a continuous threat to public health if wildlife trade is not effectively controlled.

Transmission dynamics of 2019 novel coronavirus (2019-nCoV)

Background Since December 29, 2019, pneumonia infection with 2019-nCoV has rapidly spread out from Wuhan, Hubei Province, China to most others provinces and other counties. However, the transmission dynamics of 2019-nCoV remain unclear. Methods Data of confirmed 2019-nCoV cases before January 23, 2020 were collected from medical records, epidemiological investigations or official websites. Data of severe acute respiratory syndrome (SARS) cases in Guangdong Province during 2002-2003 were obtained from Guangdong Provincial Center for Disease Control and Prevention (GDCDC). Exponential Growth (EG) and maximum likelihood estimation (ML) were applied to estimate the reproductive number (R) of 2019-nCoV and SARS. Findings As of January 23, 2020, a total of 830 confirmed 2019-nCoV cases were identified across China, and 9 cases were reported overseas. The average incubation duration of 2019-nCoV infection was 4.8days. The average period from onset of symptoms to isolation of 2019-nCoV and SARS cases were 2.9 and 4.2 days, respectively. The R values of 2019-nCoV were 2.90 (95%CI: 2.32-3.63) and 2.92 (95%CI: 2.28-3.67) estimated using EG and ML respectively, while the corresponding R values of SARS-CoV were 1.77 (95%CI: 1.37-2.27) and 1.85 (95%CI: 1.32-2.49). We observe a decreasing trend of the period from onset to isolation and R values of both 2019-nCoV and SARS-CoV. Interpretation The 2019-nCoV may have a higher pandemic risk than SARS broken out in 2003. The implemented public-health efforts have significantly decreased the pandemic risk of 2019-nCoV. However, more rigorous control and prevention strategies and measures to contain its further spread. Funding National Key Research and Development Program of China, Science and Technology Program of Guangdong Province, and Guangzhou Science and technology Plan Project.

COVID-2019: update on epidemiology, disease spread and management.

Overlapping and discrete aspects of the pathology and pathogenesis of the emerging human pathogenic coronaviruses SARS-CoV, MERS-CoV, and 2019-nCoV

First reported from Wuhan, The People's Republic of China, on 31 December 2019, the ongoing outbreak of a novel coronavirus (2019-nCoV) causes great global concerns. Based on the advice of the International Health Regulations Emergency Committee and the fact that to date 24 other countries also reported cases, the WHO Director-General declared that the outbreak of 2019-nCoV constitutes a Public Health Emergency of International Concern on 30 January 2020. Together with the other two highly pathogenic coronaviruses, the severe acute respiratory syndrome coronavirus (SARS-CoV) and Middle East respiratory syndrome coronavirus (MERS-CoV), 2019-nCov and other yet to be identified coronaviruses pose a global threat to public health. In this mini-review, we provide a brief introduction to the pathology and pathogenesis of SARS-CoV and MERS-CoV and extrapolate this knowledge to the newly identified 2019-nCoV.

Dynamical asymmetry exposes 2019-nCoV prefusion spike

The novel coronavirus (2019-nCoV) spike protein is a smart molecular machine that instigates the entry of coronavirus to the host cell causing the COVID-19 pandemic. In this study, a structural-topology based model Hamiltonian of C3 symmetric trimeric spike is developed to explore its complete conformational energy landscape using molecular dynamic simulations. The study finds 2019-nCoV to adopt a unique strategy by undertaking a dynamic conformational asymmetry induced by a few unique inter-chain interactions. This results in two prevalent asymmetric structures of spike where one or two spike heads lifted up undergoing a dynamic transition likely to enhance rapid recognition of the host-cell receptor turning on its high-infectivity. The crucial interactions identified in this study are anticipated to potentially affect the efficacy of therapeutic targets. One Sentence Summary Inter-chain-interaction driven rapid symmetry breaking strategy adopted by the prefusion trimeric spike protein likely to make 2019-nCoV highly infective.