Jun 9, 2020Paper

Nucleotide Analogues as Inhibitors of SARS-CoV-2 Polymerase

BioRxiv : the Preprint Server for Biology
M. ChienJingyue Ju

Abstract

SARS-CoV-2, a member of the coronavirus family, is responsible for the current COVID-19 pandemic. Based on our analysis of hepatitis C virus and coronavirus replication, and the molecular structures and activities of viral inhibitors, we previously demonstrated that three nucleotide analogues inhibit the SARS-CoV RNA-dependent RNA polymerase (RdRp). Here, using polymerase extension experiments, we have demonstrated that the active triphosphate form of Sofosbuvir (a key component of the FDA approved hepatitis C drug EPCLUSA), is incorporated by SARS-CoV-2 RdRp, and blocks further incorporation. Using the same molecular insight, we selected the active triphosphate forms of three other anti-viral agents, Alovudine, AZT (an FDA approved HIV/AIDS drug) and Tenofovir alafenamide (TAF, an FDA approved drug for HIV and hepatitis B) for evaluation as inhibitors of SARS-CoV-2 RdRp. We demonstrated the ability of these three viral polymerase inhibitors, 3'-fluoro-3'-deoxythymidine triphosphate, 3'-azido-3'-deoxythymidine triphosphate and Tenofovir diphosphate (the active triphosphate forms of Alovudine, AZT and TAF, respectively) to be incorporated by SARS-CoV-2 RdRp, where they also terminate further polymerase extension. These results o...Continue Reading

Citations

Sep 3, 2020·Indian Journal of Pharmacology·Rohit Gupta, Puneet Dhamija
Sep 6, 2020·Pharmacological Reports : PR·Thakur Uttam SinghRaj Kumar Singh
Nov 4, 2020·Medwave·Alfonso Agustín Prieto Pozo, Francisco Luis Daniel Salvador Sagüez
Jan 14, 2021·The Biochemical Journal·George M Burslem
Mar 27, 2021·International Journal of Biological Macromolecules·Suliman KhanMojtaba Falahati

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