Analysis of the mutation dynamics of SARS CoV 2 reveals the spread history and emergence of RBD mutant with lower ACE2 binding affinity
Monitoring the mutation dynamics of SARS CoV 2 is critical for the development of effective approaches to contain the pathogen. By analyzing 106 SARS CoV 2 and 39 SARS genome sequences, we provided direct genetic evidence that SARS CoV 2 has a much lower mutation rate than SARS. Minimum Evolution phylogeny analysis revealed the putative original status of SARS CoV 2 and the early stage spread history. The discrepant phylogenies for the spike protein and its receptor binding domain proved a previously reported structural rearrangement prior to the emergence of SARS CoV 2. Despite that we found the spike glycoprotein of SARS CoV 2 is particularly more conserved, we identified a receptor binding domain mutation that leads to weaker ACE2 binding capability based on in silico simulation, which concerns a SARS CoV 2 sample collected on 27th January 2020 from India. This represents the first report of a significant SARS CoV 2 mutant, and requires attention from researchers working on vaccine development around the world. Highlights Based on the currently available genome sequence data, we provided direct genetic evidence that the SARS COV 2 genome has a much lower mutation rate and genetic diversity than SARS during the 2002 2003 outbreak. The spike (S) protein encoding gene of SARS COV 2 is found relatively more conserved than other protein encoding genes, which is a good indication for the ongoing antiviral drug and vaccine development. Minimum Evolution phylogeny analysis revealed the putative original status of SARS CoV 2 and the early stage spread history. We confirmed a previously reported rearrangement in the S protein arrangement of SARS COV 2, and propose that this rearrangement should have occurred between human SARS CoV and a bat SARS CoV, at a time point much earlier before SARS COV 2 transmission to human. We provided first evidence that a mutated SARS COV 2 with reduced human ACE2 receptor binding affinity have emerged in India based on a sample collected on 27th January 2020.