tetano
Editor, Senior Moderator
Nat Commun
. 2020 Sep 4;11(1):4417.
doi: 10.1038/s41467-020-18233-x.
Both Boceprevir and GC376 efficaciously inhibit SARS-CoV-2 by targeting its main protease
Lifeng Fu[SUP] 1 2 [/SUP], Fei Ye[SUP] 3 [/SUP], Yong Feng[SUP] 1 4 [/SUP], Feng Yu[SUP] 5 [/SUP], Qisheng Wang[SUP] 5 [/SUP], Yan Wu[SUP] 6 7 [/SUP], Cheng Zhao[SUP] 1 [/SUP], Huan Sun[SUP] 1 [/SUP], Baoying Huang[SUP] 3 [/SUP], Peihua Niu[SUP] 3 [/SUP], Hao Song[SUP] 6 [/SUP], Yi Shi[SUP] 1 2 8 [/SUP], Xuebing Li[SUP] 9 10 [/SUP], Wenjie Tan[SUP] 11 [/SUP], Jianxun Qi[SUP] 12 13 [/SUP], George Fu Gao[SUP] 14 [/SUP]
Affiliations
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[SUP]pro[/SUP], 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[SUP]pro[/SUP]. 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[SUP]pro[/SUP] 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.
. 2020 Sep 4;11(1):4417.
doi: 10.1038/s41467-020-18233-x.
Both Boceprevir and GC376 efficaciously inhibit SARS-CoV-2 by targeting its main protease
Lifeng Fu[SUP] 1 2 [/SUP], Fei Ye[SUP] 3 [/SUP], Yong Feng[SUP] 1 4 [/SUP], Feng Yu[SUP] 5 [/SUP], Qisheng Wang[SUP] 5 [/SUP], Yan Wu[SUP] 6 7 [/SUP], Cheng Zhao[SUP] 1 [/SUP], Huan Sun[SUP] 1 [/SUP], Baoying Huang[SUP] 3 [/SUP], Peihua Niu[SUP] 3 [/SUP], Hao Song[SUP] 6 [/SUP], Yi Shi[SUP] 1 2 8 [/SUP], Xuebing Li[SUP] 9 10 [/SUP], Wenjie Tan[SUP] 11 [/SUP], Jianxun Qi[SUP] 12 13 [/SUP], George Fu Gao[SUP] 14 [/SUP]
Affiliations
- PMID: 32887884
- DOI: 10.1038/s41467-020-18233-x
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[SUP]pro[/SUP], 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[SUP]pro[/SUP]. 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[SUP]pro[/SUP] 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.