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

Author

Listed:
  • Lifeng Fu

    (CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences
    Center for Influenza Research and Early Warning (CASCIRE), CAS-TWAS Center of Excellence for Emerging Infectious Disease (CEEID), 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
    University of 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
    Department of Pathogen Microbiology, School of Basic Medical Sciences, Capital Medical University)

  • 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
    Center for Influenza Research and Early Warning (CASCIRE), CAS-TWAS Center of Excellence for Emerging Infectious Disease (CEEID), Chinese Academy of Sciences
    Savaid Medical School, University of Chinese Academy of Sciences)

  • Xuebing Li

    (CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences
    University of 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
    Savaid Medical School, University of Chinese Academy of Sciences)

  • George Fu Gao

    (CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences)

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.

Suggested Citation

  • 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 & George Fu Gao, 2020. "Both Boceprevir and GC376 efficaciously inhibit SARS-CoV-2 by targeting its main protease," Nature Communications, Nature, vol. 11(1), pages 1-8, December.
    • Handle: RePEc:nat:natcom:v:11:y:2020:i:1:d:10.1038_s41467-020-18233-x
    DOI: 10.1038/s41467-020-18233-x
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    Cited by:

    1. Jaeyong Lee & Calem Kenward & Liam J. Worrall & Marija Vuckovic & Francesco Gentile & Anh-Tien Ton & Myles Ng & Artem Cherkasov & Natalie C. J. Strynadka & Mark Paetzel, 2022. "X-ray crystallographic characterization of the SARS-CoV-2 main protease polyprotein cleavage sites essential for viral processing and maturation," Nature Communications, Nature, vol. 13(1), pages 1-13, December.
    2. Xiangrui Jiang & Haixia Su & Weijuan Shang & Feng Zhou & Yan Zhang & Wenfeng Zhao & Qiumeng Zhang & Hang Xie & Lei Jiang & Tianqing Nie & Feipu Yang & Muya Xiong & Xiaoxing Huang & Minjun Li & Ping Ch, 2023. "Structure-based development and preclinical evaluation of the SARS-CoV-2 3C-like protease inhibitor simnotrelvir," Nature Communications, Nature, vol. 14(1), pages 1-15, December.
    3. Daniel W. Kneller & Hui Li & Gwyndalyn Phillips & Kevin L. Weiss & Qiu Zhang & Mark A. Arnould & Colleen B. Jonsson & Surekha Surendranathan & Jyothi Parvathareddy & Matthew P. Blakeley & Leighton Coa, 2022. "Covalent narlaprevir- and boceprevir-derived hybrid inhibitors of SARS-CoV-2 main protease," Nature Communications, Nature, vol. 13(1), pages 1-11, December.

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