Rapid incorporation of Favipiravir by the fast and permissive viral RNA polymerase complex results in SARS-CoV-2 lethal mutagenesis - Archive ouverte HAL Access content directly
Journal Articles Nature Communications Year : 2020

Rapid incorporation of Favipiravir by the fast and permissive viral RNA polymerase complex results in SARS-CoV-2 lethal mutagenesis

(1) , (1) , (1) , (2) , (3) , (3) , (1) , (1) , (1) , (2) , (3) , (4) , (1)
1
2
3
4
Franck Touret
Bruno Coutard

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.
Fichier principal
Vignette du fichier
s41467-020-18463-z.pdf (1.77 Mo) Télécharger le fichier
Origin : Publication funded by an institution

Dates and versions

inserm-03052188 , version 1 (11-12-2020)

Licence

Attribution - CC BY 4.0

Identifiers

Cite

Ashleigh Shannon, Barbara Selisko, Nhung-Thi-Tuyet Le, Johanna Huchting, Franck Touret, et al.. Rapid incorporation of Favipiravir by the fast and permissive viral RNA polymerase complex results in SARS-CoV-2 lethal mutagenesis. Nature Communications, 2020, 11 (1), pp.4682. ⟨10.1038/s41467-020-18463-z⟩. ⟨inserm-03052188⟩
110 View
92 Download

Altmetric

Share

Gmail Facebook Twitter LinkedIn More