Authors: Menendez-Arias L

PMID: 34118236 PMCID: PMC8188802 DOI: 10.1016/j.jbc.2021.100867


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