tetano
Editor, Senior Moderator
Nat Commun
. 2020 Sep 17;11(1):4682.
doi: 10.1038/s41467-020-18463-z.
Rapid incorporation of Favipiravir by the fast and permissive viral RNA polymerase complex results in SARS-CoV-2 lethal mutagenesis
Ashleigh Shannon[SUP] 1 [/SUP], Barbara Selisko[SUP] 1 [/SUP], Nhung-Thi-Tuyet Le[SUP] 1 [/SUP], Johanna Huchting[SUP] 2 [/SUP], Franck Touret[SUP] 3 [/SUP], G?raldine Piorkowski[SUP] 3 [/SUP], V?ronique Fattorini[SUP] 1 [/SUP], Fran?ois Ferron[SUP] 1 [/SUP], Etienne Decroly[SUP] 1 [/SUP], Chris Meier[SUP] 2 [/SUP], Bruno Coutard[SUP] 3 [/SUP], Olve Peersen[SUP] 4 [/SUP], Bruno Canard[SUP] 5 [/SUP]
Affiliations
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. We demonstrate here that Favipiravir predominantly exerts an antiviral effect through 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.
. 2020 Sep 17;11(1):4682.
doi: 10.1038/s41467-020-18463-z.
Rapid incorporation of Favipiravir by the fast and permissive viral RNA polymerase complex results in SARS-CoV-2 lethal mutagenesis
Ashleigh Shannon[SUP] 1 [/SUP], Barbara Selisko[SUP] 1 [/SUP], Nhung-Thi-Tuyet Le[SUP] 1 [/SUP], Johanna Huchting[SUP] 2 [/SUP], Franck Touret[SUP] 3 [/SUP], G?raldine Piorkowski[SUP] 3 [/SUP], V?ronique Fattorini[SUP] 1 [/SUP], Fran?ois Ferron[SUP] 1 [/SUP], Etienne Decroly[SUP] 1 [/SUP], Chris Meier[SUP] 2 [/SUP], Bruno Coutard[SUP] 3 [/SUP], Olve Peersen[SUP] 4 [/SUP], Bruno Canard[SUP] 5 [/SUP]
Affiliations
- PMID: 32943628
- DOI: 10.1038/s41467-020-18463-z
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. We demonstrate here that Favipiravir predominantly exerts an antiviral effect through 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.