1. Academic Validation
  2. Both Boceprevir and GC376 efficaciously inhibit SARS-CoV-2 by targeting its main protease

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

  • Nat Commun. 2020 Sep 4;11(1):4417. doi: 10.1038/s41467-020-18233-x.
Lifeng Fu  # 1 2 Fei Ye  # 3 Yong Feng  # 1 4 Feng Yu 5 Qisheng Wang 5 Yan Wu 6 7 Cheng Zhao 1 Huan Sun 1 Baoying Huang 3 Peihua Niu 3 Hao Song 6 Yi Shi 1 2 8 Xuebing Li 9 10 Wenjie Tan 11 Jianxun Qi 12 13 George Fu Gao 14
Affiliations

Affiliations

  • 1 CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, 100101, Beijing, China.
  • 2 Center for Influenza Research and Early Warning (CASCIRE), CAS-TWAS Center of Excellence for Emerging Infectious Disease (CEEID), Chinese Academy of Sciences, 100101, Beijing, China.
  • 3 NHC Key Laboratory of Biosafety, National Institute for Viral Disease Control & Prevention, Chinese Center for Disease Control and Prevention, China CDC, 102206, Beijing, China.
  • 4 University of Chinese Academy of Sciences, 100049, Beijing, China.
  • 5 Shanghai Synchrotron Radiation Facility, Shanghai Advanced Research Institute, Chinese Academy of Sciences, 201204, Shanghai, China.
  • 6 Research Network of Immunity and Health (RNIH), Beijing Institutes of Life Science, Chinese Academy of Sciences, 100101, Beijing, China.
  • 7 Department of Pathogen Microbiology, School of Basic Medical Sciences, Capital Medical University, 100069, Beijing, China.
  • 8 Savaid Medical School, University of Chinese Academy of Sciences, 100049, Beijing, China.
  • 9 CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, 100101, Beijing, China. [email protected]
  • 10 University of Chinese Academy of Sciences, 100049, Beijing, China. [email protected]
  • 11 NHC Key Laboratory of Biosafety, National Institute for Viral Disease Control & Prevention, Chinese Center for Disease Control and Prevention, China CDC, 102206, Beijing, China. [email protected]
  • 12 CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, 100101, Beijing, China. [email protected]
  • 13 Savaid Medical School, University of Chinese Academy of Sciences, 100049, Beijing, China. [email protected]
  • 14 CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, 100101, Beijing, China. [email protected]
  • # Contributed equally.
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.

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