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Decoding molnupiravir-induced mutagenesis in SARS-CoV-2

https://doi.org/10.1016/j.jbc.2021.100867Get rights and content
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Molnupiravir, a prodrug of the nucleoside derivative β-D-N4-hydroxycytidine (NHC), is currently in clinical trials for COVID-19 therapy. However, the biochemical mechanisms involved in molnupiravir-induced mutagenesis had not been explored. In a recent study, Gordon et al. demonstrated that NHC can be incorporated into viral RNA and subsequently extended and used as template for RNA-dependent RNA synthesis, proposing a mutagenesis model consistent with available virological evidence. Their study uncovers molecular mechanisms by which molnupiravir drives SARS-CoV-2 into error catastrophe.

Keywords

molnupiravir
SARS-CoV-2
COVID-19
RNA polymerase
lethal mutagenesis
antiviral drug

Abbreviations

COVID-19
coronavirus infectious disease 2019
MERS-CoV
Middle East respiratory syndrome coronavirus
NHC
β-D-N4-hydroxycytidine
RdRp
RNA-dependent RNA polymerase
rNTP
ribonucleoside triphosphate
SARS-CoV
severe acute respiratory syndrome coronavirus

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