Repurposing Molnupiravir for COVID-19: The Mechanisms of Antiviral Activity

Viruses. 2022 Jun 20;14(6):1345. doi: 10.3390/v14061345.

Abstract

Molnupiravir is a β-d-N4-hydroxycytidine-5'-isopropyl ester (NHC) compound that exerts antiviral activity against various RNA viruses such as influenza, SARS, and Ebola viruses. Thus, the repurposing of Molnupiravir has gained significant attention for combatting infection with SARS-CoV-2, the etiological agent of COVID-19. Recently, Molnupiravir was granted authorization for the treatment of mild-to-moderate COVID-19 in adults. Findings from in vitro experiments, in vivo studies and clinical trials reveal that Molnupiravir is effective against SARS-CoV-2 by inducing viral RNA mutagenesis, thereby giving rise to mutated complementary RNA strands that generate non-functional viruses. To date, the data collectively suggest that Molnupiravir possesses promising antiviral activity as well as favorable prophylactic efficacy, attributed to its effective mutagenic property of disrupting viral replication. This review discusses the mechanisms of action of Molnupiravir and highlights its clinical utility by disabling SARS-CoV-2 replication, thereby ameliorating COVID-19 severity. Despite relatively few short-term adverse effects thus far, further detailed clinical studies and long-term pharmacovigilance are needed in view of its mutagenic effects.

Keywords: COVID-19; Molnupiravir; N4-hydroxycytidine; NHC; SARS-CoV-2; antiviral; repositioning; repurposing.

Publication types

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

MeSH terms

  • Antiviral Agents / pharmacology
  • Antiviral Agents / therapeutic use
  • COVID-19 Drug Treatment*
  • Cytidine / analogs & derivatives
  • Humans
  • Hydroxylamines
  • SARS-CoV-2

Substances

  • Antiviral Agents
  • Hydroxylamines
  • Cytidine
  • molnupiravir

Grants and funding

This publication was supported by internal funds to Sunil K. Lal from the School of Science, Monash University Malaysia (SoS Strategic Grant 2020), and to Vincent T. K. Chow from the National University of Singapore.