Abstract
The ongoing Corona Virus Disease 2019 (COVID-19) pandemic, caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), has emphasized the urgent need for antiviral therapeutics. The viral RNA-dependent-RNA-polymerase (RdRp) is a promising target with polymerase inhibitors successfully used for the treatment of several viral diseases. Here we show that Favipiravir exerts an antiviral effect as a nucleotide analogue through a combination of chain termination, slowed RNA synthesis and lethal mutagenesis. The SARS-CoV RdRp complex is at least 10-fold more active than any other viral RdRp known. It possesses both unusually high nucleotide incorporation rates and high-error rates allowing facile insertion of Favipiravir into viral RNA, provoking C-to-U and G-to-A transitions in the already low cytosine content SARS-CoV-2 genome. The coronavirus RdRp complex represents an Achilles heel for SARS-CoV, supporting nucleoside analogues as promising candidates for the treatment of COVID-19.
Citations
Aug 12, 2020·Reviews in Medical Virology·Coralie ValleEtienne Decroly
Oct 1, 2020·Virologica Sinica·Wenyi GuanQiwei Zhang
Sep 10, 2020·International Journal of Molecular Sciences·Neelu BatraAi-Ming Yu
Oct 11, 2020·Proceedings of the National Academy of Sciences of the United States of America·Suzanne J F KapteinLeen Delang
Oct 31, 2020·Antimicrobial Agents and Chemotherapy·Gaofei LuWen Xiong
Dec 30, 2020·Expert Review of Anti-infective Therapy·Seyed MohammadReza HashemianAli Akbar Velayati
Jan 12, 2021·Topics in Current Chemistry·Dingzhong LiRenhua Qiu
Jan 27, 2021·Infectious Diseases and Therapy·Nicholas ReboldMichael Rybak
Dec 9, 2020·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Francesca PicarazziMattia Mori
Oct 30, 2020·Nature Reviews. Microbiology·Philip V'kovskiVolker Thiel
Oct 24, 2020·Microorganisms·Mitsuru SadaHirokazu Kimura
Mar 19, 2021·International Immunopharmacology·Masoud Solaymani-DodaranJavad Moazen
Mar 23, 2021·Oncology Reviews·Hasan KobatShereen Nabhani-Gebara
Mar 23, 2021·Frontiers in Microbiology·Ahmad F EweasAhmed S Abdel-Moneim
Mar 26, 2021·Frontiers in Molecular Biosciences·Karthik VivekanandhanMuthupandian Saravanan
May 1, 2021·Viruses·Robert J GeraghtyLaurent F Bonnac
Jun 15, 2021·Curēus·Dhigishaba M Jadeja, Nirmit R Patel
Jul 5, 2021·International Immunopharmacology·Seyed MohammadReza HashemianAli Akbar Velayati
Sep 4, 2021·GeroScience·Balint Gergely SzaboUNKNOWN Saint Ladislaus COVID-19 Collaborative