Both Boceprevir and GC376 efficaciously inhibit SARS-CoV-2 by targeting its main protease

Lifeng Fu(Chinese Academy of Sciences), Fei Ye(Chinese Center For Disease Control and Prevention), Yong Feng(Chinese Academy of Sciences), Feng Yu(Chinese Academy of Sciences), Qisheng Wang(Chinese Academy of Sciences), Yan Wu(Capital Medical University), Cheng Zhao(Chinese Academy of Sciences), Huan Sun(Chinese Academy of Sciences), Baoying Huang(Chinese Center For Disease Control and Prevention), Peihua Niu(Chinese Center For Disease Control and Prevention), Hao Song(Chinese Academy of Sciences), Yi Shi(Chinese Academy of Sciences), Xuebing Li(Czech Academy of Sciences, Institute of Microbiology), Wenjie Tan(Chinese Center For Disease Control and Prevention), Jianxun Qi(Institute of Automation), George F. Gao(Chinese Academy of Sciences)
Nature Communications
September 4, 2020
10.1038/s41467-020-18233-x
Cited by 561Open Access
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Abstract

Abstract COVID-19 was declared a pandemic on March 11 by WHO, due to its great threat to global public health. The coronavirus main protease (M pro , also called 3CLpro) is essential for processing and maturation of the viral polyprotein, therefore recognized as an attractive drug target. Here we show that a clinically approved anti-HCV drug, Boceprevir, and a pre-clinical inhibitor against feline infectious peritonitis (corona) virus (FIPV), GC376, both efficaciously inhibit SARS-CoV-2 in Vero cells by targeting M pro . Moreover, combined application of GC376 with Remdesivir, a nucleotide analogue that inhibits viral RNA dependent RNA polymerase (RdRp), results in sterilizing additive effect. Further structural analysis reveals binding of both inhibitors to the catalytically active side of SARS-CoV-2 protease M pro as main mechanism of inhibition. Our findings may provide critical information for the optimization and design of more potent inhibitors against the emerging SARS-CoV-2 virus.

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