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Fu, Lifeng; Ye, Fei; Feng, Yong; Yu, Feng; Wang, Qisheng; Wu, Yan; Zhao, Cheng; Sun, Huan; Huang, Baoying; Niu, Peihua; Song, Hao; Shi, Yi; Li, Xuebing; Tan, Wenjie; Qi, Jianxun; Gao, George Fu
Nature communications, 09/2020, Volume: 11, Issue: 1Journal Article
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 , 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 . 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 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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