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Structural basis for the inhibition of COVID-19 virus main protease by carmofur, an antineoplastic drug
Zhenming Jin; Yao Zhao; Yuan Sun; Bing Zhang; Haofeng Wang; Yan Wu; Yan Zhu; Chen Zhu; Tianyu Hu; Xiaoyu Du; Yinkai Duan; Jing Yu; Xiaobao Yang; Xiuna Yang; Kailin Yang; Xiang Liu; Luke W. Guddat; Gengfu Xiao; Leike Zhang; Haitao Yang; Zihe Rao.
Affiliation
  • Zhenming Jin; Shanghai Institute for Advanced Immunochemical Studies and School of Life Science and Technology, ShanghaiTech University, Shanghai, China
  • Yao Zhao; Shanghai Institute for Advanced Immunochemical Studies and School of Life Science and Technology, ShanghaiTech University, Shanghai, China
  • Yuan Sun; State Key Laboratory of Virology, Wuhan Institute of Virology, Center for Biosafety Mega-Science, Chinese Academy of Sciences, Wuhan, China.
  • Bing Zhang; Shanghai Institute for Advanced Immunochemical Studies and School of Life Science and Technology, ShanghaiTech University, Shanghai, China
  • Haofeng Wang; Shanghai Institute for Advanced Immunochemical Studies and School of Life Science and Technology, ShanghaiTech University, Shanghai, China
  • Yan Wu; State Key Laboratory of Virology, Wuhan Institute of Virology, Center for Biosafety Mega-Science, Chinese Academy of Sciences, Wuhan, China.
  • Yan Zhu; Shanghai Institute for Advanced Immunochemical Studies and School of Life Science and Technology, ShanghaiTech University, Shanghai, China
  • Chen Zhu; Shanghai Institute for Advanced Immunochemical Studies and School of Life Science and Technology, ShanghaiTech University, Shanghai, China
  • Tianyu Hu; Shanghai Institute for Advanced Immunochemical Studies and School of Life Science and Technology, ShanghaiTech University, Shanghai, China
  • Xiaoyu Du; Shanghai Institute for Advanced Immunochemical Studies and School of Life Science and Technology, ShanghaiTech University, Shanghai, China
  • Yinkai Duan; Shanghai Institute for Advanced Immunochemical Studies and School of Life Science and Technology, ShanghaiTech University, Shanghai, China
  • Jing Yu; Shanghai Institute for Advanced Immunochemical Studies and School of Life Science and Technology, ShanghaiTech University, Shanghai, China
  • Xiaobao Yang; Shanghai Institute for Advanced Immunochemical Studies and School of Life Science and Technology, ShanghaiTech University, Shanghai, China
  • Xiuna Yang; Shanghai Institute for Advanced Immunochemical Studies and School of Life Science and Technology, ShanghaiTech University, Shanghai, China
  • Kailin Yang; Taussig Cancer Center, Cleveland Clinic, Cleveland, OH, USA
  • Xiang Liu; State Key Laboratory of Medicinal Chemical Biology, Frontiers Science Center for Cell Response, College of Life Sciences, College of Pharmacy, Nankai University
  • Luke W. Guddat; School of Chemistry and Molecular Biosciences, The University of Queensland, Brisbane, Australia
  • Gengfu Xiao; State Key Laboratory of Virology, Wuhan Institute of Virology, Center for Biosafety Mega-Science, Chinese Academy of Sciences, Wuhan, China
  • Leike Zhang; State Key Laboratory of Virology, Wuhan Institute of Virology, Center for Biosafety Mega-Science, Chinese Academy of Sciences, Wuhan, China
  • Haitao Yang; Shanghai Institute for Advanced Immunochemical Studies and School of Life Science and Technology, ShanghaiTech University, Shanghai, China
  • Zihe Rao; Shanghai Institute for Advanced Immunochemical Studies and School of Life Science and Technology, ShanghaiTech University, Shanghai, China
Preprint in English | bioRxiv | ID: ppbiorxiv-033233
ABSTRACT
The antineoplastic drug Carmofur was shown to inhibit SARS-CoV-2 main protease (Mpro). Here the X-ray crystal structure of Mpro in complex with Carmofur reveals that the carbonyl reactive group of Carmofur is covalently bound to catalytic Cys145, whereas its fatty acid tail occupies the hydrophobic S2 subsite. Carmofur inhibits viral replication in cells (EC50 = 24.30 M) and it is a promising lead compound to develop new antiviral treatment for COVID-19.
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Full text: Available Collection: Preprints Database: bioRxiv Language: English Year: 2020 Document type: Preprint
Fulltext
Add to My VHL
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Full text: Available Collection: Preprints Database: bioRxiv Language: English Year: 2020 Document type: Preprint