Decoding molnupiravir-induced mutagenesis in SARS-CoV-2

J Biol Chem. 2021 Jul;297(1):100867. doi: 10.1016/j.jbc.2021.100867. Epub 2021 Jun 9.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antiviral Agents / pharmacology*
  • COVID-19 / virology*
  • Cytidine / analogs & derivatives*
  • Cytidine / pharmacology
  • Humans
  • Hydroxylamines / pharmacology*
  • Point Mutation / drug effects
  • RNA, Viral / genetics
  • SARS-CoV-2 / drug effects*
  • SARS-CoV-2 / genetics*
  • SARS-CoV-2 / metabolism

Substances

  • Antiviral Agents
  • Hydroxylamines
  • RNA, Viral
  • Cytidine
  • molnupiravir