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Pré-Publication, Document De Travail Année : 2020

Favipiravir strikes the SARS-CoV-2 at its Achilles heel, the RNA polymerase

Résumé

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.
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Dates et versions

hal-02890576 , version 1 (18-12-2020)

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A. Shannon, B. Selisko, Ntt Le, J. Huchting, F. Touret, et al.. Favipiravir strikes the SARS-CoV-2 at its Achilles heel, the RNA polymerase. 2020. ⟨hal-02890576⟩
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