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


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.

SUBMITTER: Shannon A 

PROVIDER: S-EPMC7263509 | biostudies-literature | 2020 May

REPOSITORIES: biostudies-literature

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

Shannon A A   Selisko B B   Le Ntt N   Huchting J J   Touret F F   Piorkowski G G   Fattorini V V   Ferron F F   Decroly E E   Meier C C   Coutard B B   Peersen O O   Canard B B  

bioRxiv : the preprint server for biology 20200515


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 l  ...[more]

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