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Structural basis for the inhibition of SARS-CoV-2 main protease by antineoplastic drug carmofur.
Jin, Zhenming; Zhao, Yao; Sun, Yuan; Zhang, Bing; Wang, Haofeng; Wu, Yan; Zhu, Yan; Zhu, Chen; Hu, Tianyu; Du, Xiaoyu; Duan, Yinkai; Yu, Jing; Yang, Xiaobao; Yang, Xiuna; Yang, Kailin; Liu, Xiang; Guddat, Luke W; Xiao, Gengfu; Zhang, Leike; Yang, Haitao; Rao, Zihe.
  • Jin Z; Shanghai Institute for Advanced Immunochemical Studies and School of Life Science and Technology, ShanghaiTech University, Shanghai, China.
  • Zhao Y; Laboratory of Structural Biology, School of Life Sciences and School of Medicine, Tsinghua University, Beijing, China.
  • Sun Y; Shanghai Institute for Advanced Immunochemical Studies and School of Life Science and Technology, ShanghaiTech University, Shanghai, China.
  • Zhang B; State Key Laboratory of Virology, Wuhan Institute of Virology, Center for Biosafety Mega-Science, Chinese Academy of Sciences, Wuhan, China.
  • Wang H; Shanghai Institute for Advanced Immunochemical Studies and School of Life Science and Technology, ShanghaiTech University, Shanghai, China.
  • Wu Y; Shanghai Institute for Advanced Immunochemical Studies and School of Life Science and Technology, ShanghaiTech University, Shanghai, China.
  • Zhu Y; School of Life Sciences, Tianjin University, Tianjin, China.
  • Zhu C; State Key Laboratory of Virology, Wuhan Institute of Virology, Center for Biosafety Mega-Science, Chinese Academy of Sciences, Wuhan, China.
  • Hu T; Shanghai Institute for Advanced Immunochemical Studies and School of Life Science and Technology, ShanghaiTech University, Shanghai, China.
  • Du X; Shanghai Institute for Advanced Immunochemical Studies and School of Life Science and Technology, ShanghaiTech University, Shanghai, China.
  • Duan Y; Shanghai Institute for Advanced Immunochemical Studies and School of Life Science and Technology, ShanghaiTech University, Shanghai, China.
  • Yu J; Shanghai Institute for Advanced Immunochemical Studies and School of Life Science and Technology, ShanghaiTech University, Shanghai, China.
  • Yang X; Laboratory of Structural Biology, School of Life Sciences and School of Medicine, Tsinghua University, Beijing, China.
  • Yang X; Shanghai Institute for Advanced Immunochemical Studies and School of Life Science and Technology, ShanghaiTech University, Shanghai, China.
  • Yang K; Shanghai Institute for Advanced Immunochemical Studies and School of Life Science and Technology, ShanghaiTech University, Shanghai, China.
  • Liu X; Shanghai Institute for Advanced Immunochemical Studies and School of Life Science and Technology, ShanghaiTech University, Shanghai, China.
  • Guddat LW; Shanghai Institute for Advanced Immunochemical Studies and School of Life Science and Technology, ShanghaiTech University, Shanghai, China.
  • Xiao G; Taussig Cancer Center, Cleveland Clinic, Cleveland, OH, USA.
  • Zhang L; State Key Laboratory of Medicinal Chemical Biology, Frontiers Science Center for Cell Response, College of Life Sciences, College of Pharmacy, Nankai University, Tianjin, China.
  • Yang H; School of Chemistry and Molecular Biosciences, the University of Queensland, Brisbane, Australia.
  • Rao Z; State Key Laboratory of Virology, Wuhan Institute of Virology, Center for Biosafety Mega-Science, Chinese Academy of Sciences, Wuhan, China.
Nat Struct Mol Biol ; 27(6): 529-532, 2020 06.
Article in English | MEDLINE | ID: covidwho-222247
ABSTRACT
The antineoplastic drug carmofur is shown to inhibit the 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 µM) and is a promising lead compound to develop new antiviral treatment for COVID-19.
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Full text: Available Collection: International databases Database: MEDLINE Main subject: Cysteine Endopeptidases / Viral Nonstructural Proteins / Fluorouracil / Betacoronavirus Limits: Animals Language: English Journal: Nat Struct Mol Biol Journal subject: Molecular Biology Year: 2020 Document Type: Article Affiliation country: S41594-020-0440-6

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Full text: Available Collection: International databases Database: MEDLINE Main subject: Cysteine Endopeptidases / Viral Nonstructural Proteins / Fluorouracil / Betacoronavirus Limits: Animals Language: English Journal: Nat Struct Mol Biol Journal subject: Molecular Biology Year: 2020 Document Type: Article Affiliation country: S41594-020-0440-6