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

被引：38

作者：

Wang, Yining ^{[1
]}

Li, Pengfei ^{[1
]}

Solanki, Kundan ^{[2
]}

Li, Yang ^{[1
]}

Ma, Zhongren ^{[3
]}

Peppelenbosch, Maikel P. ^{[1
]}

Baig, Mirza S. ^{[2
]}

Pan, Qiuwei ^{[1
]}

机构：

[1] Erasmus MC, Univ Med Ctr, Dept Gastroenterol & Hepatol, Rotterdam, Netherlands

[2] Indian Inst Technol Indore IITI, Dept Biosci & Biomed Engn BSBE, Indore, India

[3] Northwest Minzu Univ, Biomed Res Ctr, Lanzhou, Peoples R China

来源：

VIROLOGY | 2021年 / 564卷

关键词：

Molnupiravir; Seasonal coronavirus; RdRp; Drug repurposing; IDENTIFICATION;

D O I：

10.1016/j.virol.2021.09.009

中图分类号：

Q93 [微生物学];

学科分类号：

071005 ; 100705 ;

摘要：

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, beta-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.

引用

页码：33 / 38

页数：6