Decoding molnupiravir-induced mutagenesis in SARS-CoV-2
Menendez-Arias, Luis
JOURNAL OF BIOLOGICAL CHEMISTRY
2021
VL / 297 - BP / - EP /
abstract
Molnupiravir, a prodrug of the nucleoside derivative beta-D-N-4-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.
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