Molnupiravir: A lethal mutagenic drug against rapidly mutating severe acute respiratory syndrome coronavirus 2-A narrative review

J Med Virol. 2022 Jul;94(7):3006-3016. doi: 10.1002/jmv.27730. Epub 2022 Apr 2.

Abstract

Broad-spectrum antiviral agents targeting viral RNA-dependent RNA polymerase (RdRp) are expected to be a key therapeutic strategy in the ongoing coronavirus disease 2019 (COVID-19) pandemic and its future variants of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus that causes COVID-19. Molnupiravir is a nucleoside analog that in vivo experiments have been reported to inhibit the replication of SARS-CoV-2, the virus that causes COVID-19. Clinical trials of molnupiravir as a therapy for patients with mild-to-moderate COVID-19 also suggest its significant therapeutic efficacy in comparison to placebo. Molnupiravir is lethally mutagenic against viral RNA, but its effect on host cell DNA is being questioned. Herein, the safety concerns of molnupiravir are discussed with recent findings from published reports and clinical trials. The unchanged efficacy of molnupiravir against mutated SARS-CoV-2 variants is also highlighted. With its administration via the oral route, molnupiravir is expected to turn the tide of the COVID-19 pandemic.

Keywords: COVID-19; EIDD-2801; error catastrophe; mutagenesis; β-d-N4-hydroxycytidine.

Publication types

  • Review
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antiviral Agents / adverse effects
  • COVID-19 Drug Treatment*
  • Cytidine / analogs & derivatives
  • Humans
  • Hydroxylamines
  • Mutagens / pharmacology
  • Pandemics
  • Pharmaceutical Preparations
  • SARS-CoV-2*

Substances

  • Antiviral Agents
  • Hydroxylamines
  • Mutagens
  • Pharmaceutical Preparations
  • Cytidine
  • molnupiravir

Supplementary concepts

  • SARS-CoV-2 variants