Both Boceprevir and GC376 efficaciously inhibit SARS-CoV-2 by targeting its main protease
Lifeng Fu,
Fei Ye,
Yong Feng,
Feng Yu,
Qisheng Wang,
Yan Wu,
Cheng Zhao,
Huan Sun,
Baoying Huang,
Peihua Niu,
Hao Song,
Yi Shi,
Xuebing Li (),
Wenjie Tan (),
Jianxun Qi () and
George Fu Gao ()
Additional contact information
Lifeng Fu: CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences
Fei Ye: NHC Key Laboratory of Biosafety, National Institute for Viral Disease Control & Prevention, Chinese Center for Disease Control and Prevention, China CDC
Yong Feng: CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences
Feng Yu: Shanghai Synchrotron Radiation Facility, Shanghai Advanced Research Institute, Chinese Academy of Sciences
Qisheng Wang: Shanghai Synchrotron Radiation Facility, Shanghai Advanced Research Institute, Chinese Academy of Sciences
Yan Wu: Research Network of Immunity and Health (RNIH), Beijing Institutes of Life Science, Chinese Academy of Sciences
Cheng Zhao: CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences
Huan Sun: CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences
Baoying Huang: NHC Key Laboratory of Biosafety, National Institute for Viral Disease Control & Prevention, Chinese Center for Disease Control and Prevention, China CDC
Peihua Niu: NHC Key Laboratory of Biosafety, National Institute for Viral Disease Control & Prevention, Chinese Center for Disease Control and Prevention, China CDC
Hao Song: Research Network of Immunity and Health (RNIH), Beijing Institutes of Life Science, Chinese Academy of Sciences
Yi Shi: CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences
Xuebing Li: CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences
Wenjie Tan: NHC Key Laboratory of Biosafety, National Institute for Viral Disease Control & Prevention, Chinese Center for Disease Control and Prevention, China CDC
Jianxun Qi: CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences
George Fu Gao: CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences
Nature Communications, 2020, vol. 11, issue 1, 1-8
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 (Mpro, 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 Mpro. 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 Mpro 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.
Date: 2020
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Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:11:y:2020:i:1:d:10.1038_s41467-020-18233-x
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DOI: 10.1038/s41467-020-18233-x
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