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Viral polymerase binding and broad-spectrum antiviral activity of molnupiravir against human seasonal coronaviruses.
Wang, Yining; Li, Pengfei; Solanki, Kundan; Li, Yang; Ma, Zhongren; Peppelenbosch, Maikel P; Baig, Mirza S; Pan, Qiuwei.
  • Wang Y; Department of Gastroenterology and Hepatology, Erasmus MC-University Medical Center, Rotterdam, the Netherlands.
  • Li P; Department of Gastroenterology and Hepatology, Erasmus MC-University Medical Center, Rotterdam, the Netherlands.
  • Solanki K; Department of Biosciences and Biomedical Engineering (BSBE), Indian Institute of Technology Indore (IITI), Simrol, Indore, India.
  • Li Y; Department of Gastroenterology and Hepatology, Erasmus MC-University Medical Center, Rotterdam, the Netherlands.
  • Ma Z; Biomedical Research Center, Northwest Minzu University, Lanzhou, China.
  • Peppelenbosch MP; Department of Gastroenterology and Hepatology, Erasmus MC-University Medical Center, Rotterdam, the Netherlands.
  • Baig MS; Department of Biosciences and Biomedical Engineering (BSBE), Indian Institute of Technology Indore (IITI), Simrol, Indore, India. Electronic address: msb.iit@iiti.ac.in.
  • Pan Q; Department of Gastroenterology and Hepatology, Erasmus MC-University Medical Center, Rotterdam, the Netherlands. Electronic address: q.pan@erasmusmc.nl.
Virology ; 564: 33-38, 2021 12.
Article in English | MEDLINE | ID: covidwho-1447220
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, ß-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 that the great potential of repurposing molnupiravir for treating seasonal coronavirus infected patients.
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Full text: Available Collection: International databases Database: MEDLINE Main subject: Coronavirus Infections / Coronavirus 229E, Human / Coronavirus OC43, Human / Cytidine / Coronavirus NL63, Human / Hydroxylamines Type of study: Experimental Studies Limits: Humans Language: English Journal: Virology Year: 2021 Document Type: Article Affiliation country: J.virol.2021.09.009

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Full text: Available Collection: International databases Database: MEDLINE Main subject: Coronavirus Infections / Coronavirus 229E, Human / Coronavirus OC43, Human / Cytidine / Coronavirus NL63, Human / Hydroxylamines Type of study: Experimental Studies Limits: Humans Language: English Journal: Virology Year: 2021 Document Type: Article Affiliation country: J.virol.2021.09.009