Research
Sotrovimab is being evaluated in the following clinical trials:
Clinical trial number NCT04545060 for "COMET-ICE" at ClinicalTrials.gov
Clinical trial number NCT04779879 for "COMET-PEAK" at ClinicalTrials.gov
Clinical trial number NCT04501978 for "ACTIV-3-TICO" at ClinicalTrials.gov
Clinical trial number NCT04634409 for "BLAZE-4" at ClinicalTrials.govIn March 2022, Australian virologists observed that sotrovimab may cause a drug-resistant mutation. References
External links
"Sotrovimab". Drug Information Portal. U.S. National Library of Medicine. Clinical trial number NCT04545060 for "VIR-7831 for the Early Treatment of COVID-19 in Outpatients (COMET-ICE)" at ClinicalTrials.gov
Australian Public Assessment Report: Sotrovimab. Therapeutic Goods Administration (TGA) (Report). 20 August 2021.
Azacitidine is a ribonucleoside, so it is incorporated into RNA to a larger extent than into DNA. In contrast, decitabine (5-aza-2-deoxycytidine) is a deoxyribonucleoside, so it can only incorporate into DNA. Azacitidines incorporation into RNA leads to the disassembly of polyribosomes, defective methylation and acceptor function of transfer RNA, and inhibition of the production of proteins. Its incorporation into DNA leads to covalent binding with DNA methyltransferases, which prevents DNA synthesis and subsequently leads to cytotoxicity. It has been shown effective against human immunodeficiency virus in vitro and human T-lymphotropic virus. Inhibition of methylation
After azanucleosides such as azacitidine have been metabolized to 5-aza-2′-deoxycytidine-triphosphate (aka, decitabine-triphosphate), they can be incorporated into DNA and azacytosine can be substituted for cytosine. Azacytosine-guanine dinucleotides are recognized as substrate by the DNA methyltransferases, which catalyze the methylation reaction by a nucleophilic attack. This results in a covalent bond between the carbon-6 atom of the cytosine ring and the enzyme. The bond is normally resolved by beta-elimination through the carbon-5 atom, but this latter reaction does not occur with azacytosine because its carbon-5 is substituted by nitrogen, leaving the enzyme covalently bound to DNA and blocking its DNA methyltransferase function. In addition, the covalent protein adduction also compromises the functionality of DNA and triggers DNA damage signaling, resulting in the degradation of trapped DNA methyltransferases. As a consequence, methylation marks become lost during DNA replication.