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

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Wang, Y., Li, P., et al. Viral polymerase binding and broad-spectrum antiviral activity of molnupiravir against human
seasonal coronaviruses, Virology (2021), doi: https://doi.org/10.1016/j.virol.2021.09.009

Recopilado por Carlos Cabrera Lozada. Director del postgrado de Medicina Materno Fetal. Universidad Central de Venezuela. ORCID: 0000-0002-3133-5183. 03/10/2021

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-N -hydroxycytidine (NHC), has similar binding affinity to RdRp of SARS-CoV-2 and seasonal HCoV-NL63, HCoV9 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.

Keywords: Molnupiravir; seasonal coronavirus; RdRp; drug repurposing

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