Cited by 46SARS-CoV-2 and COVID-19 ResearchAnimal Virus Infections StudiesRespiratory viral infections research

Viral polymerase binding and broad-spectrum antiviral activity of molnupiravir against human seasonal coronaviruses

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Wang, Yining, Li, Pengfei, Solanki, Kundan, Li, Yang, Ma, Zhongren, Peppelenbosch, Maikel P., Baig, Mirza S., Pan, Qiuwei·2021·Virology

Abstract

Endemic seasonal coronaviruses cause morbidity and mortality in a subset of patients, but no specific treatment is available. Molnupiravir is a promising pipeline antiviral drug for treating SARS-CoV-2 infection potentially by targeting RNA-dependent RNA polymerase (RdRp). This study aims to evaluate the potential of repurposing molnupiravir for treating seasonal human coronavirus (HCoV) infections. Molecular docking revealed that the active form of molnupiravir, β-D-N4-hydroxycytidine (NHC), has similar binding affinity to RdRp of SARS-CoV-2 and seasonal HCoV-NL63, HCoV-OC43 and HCoV-229E. In cell culture models, treatment of molnupiravir effectively inhibited viral replication and production of infectious viruses of the three seasonal coronaviruses. A time-of-drug-addition experiment indicates the specificity of molnupiravir in inhibiting viral components. Furthermore, combining molnupiravir with the protease inhibitor GC376 resulted in enhanced antiviral activity. Our findings highlight the great potential of repurposing molnupiravir for treating seasonal coronavirus infected patients.

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Crossref · 10.1016/j.virol.2021.09.009

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Authors
Wang, Y., Li, P., Solanki, K., Li, Y., Ma, Z., Peppelenbosch, M. P., Baig, M. S., & Pan, Q.
Affiliations
  • Erasmus MC (NL)
  • Indian Institute of Technology Indore (IN)
  • Northwest Minzu University (CN)
Corresponding author
  • Baig, Mirza S.
  • Pan, Qiuwei
Venue
Virology
Publisher
Elsevier BV
Published
2021-12
Volume
564
Pages
33-38
ISSN
0042-6822 (ISSN-L)
OpenAlex
W3204436699
Cited by
46
References
20
Citations by year
2026: 3 · 2025: 4 · 2024: 6 · 2023: 11 · 2022: 21 · 2021: 1
FWCI
3.08
Type
journal article
Language
en
Open access
Locations
  • Virology (publishedVersion, cc-by)
  • Europe PMC (PubMed Central) (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
  • EUR Research Repository (Erasmus University Rotterdam) (publishedVersion, cc-by)
  • EUR Research Repository (Erasmus University Rotterdam) (submittedVersion, cc-by)
  • RePub (Erasmus University Rotterdam) (submittedVersion, other-oa)
Funders
  • China Scholarship Council (201703250073, 201808370170, 201903250082)
  • Nederlandse Organisatie voor Wetenschappelijk Onderzoek (91719300)
Topics
  • Health Sciences › Medicine › Infectious Diseases › SARS-CoV-2 and COVID-19 Research
  • Life Sciences › Agricultural and Biological Sciences › Animal Science and Zoology › Animal Virus Infections Studies
  • Health Sciences › Medicine › Epidemiology › Respiratory viral infections research
Keywords
molnupiravir, seasonal coronaviruses, RNA-dependent RNA polymerase, drug repurposing, N4-hydroxycytidine, HCoV-NL63, HCoV-OC43, HCoV-229E, antiviral activity, viral replication inhibition, GC376, SARS-CoV-2
MeSH terms
Antiviral Agents, Common Cold, Cytidine, Humans, Hydroxylamines, Lactams, Leucine, Protein Binding, Pyrrolidines, RNA-Dependent RNA Polymerase, Seasons, Sulfonic Acids, Virus Replication, Coronavirus Infections, Coronavirus 229E, Human, Coronavirus OC43, Human, Coronavirus NL63, Human, Molecular Docking Simulation

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