High-throughput screening identifies established drugs as SARS-CoV-2 PLpro inhibitors.

Yao Zhao; Xiaoyu DU; Yinkai Duan; Xiaoyan Pan; Yifang Sun; Tian You; Lin Han; Zhenming Jin; Weijuan Shang; Jing YU; Hangtian Guo; Qianying Liu; Yan WU; Chao Peng; Jun Wang; Chenghao Zhu; Xiuna Yang; Kailin Yang; Ying Lei; Luke W Guddat; Wenqing XU; Gengfu Xiao; Lei Sun; Leike Zhang; Zihe Rao; Haitao Yang

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High-throughput screening identifies established drugs as SARS-CoV-2 PLpro inhibitors.

Author: Yao ZHAO ¹ ; Xiaoyu DU ² ; Yinkai DUAN ¹ ; Xiaoyan PAN ³ ; Yifang SUN ⁴ ; Tian YOU ¹ ; Lin HAN ⁴ ; Zhenming JIN ¹ ; Weijuan SHANG ³ ; Jing YU ¹ ; Hangtian GUO ¹ ; Qianying LIU ⁴ ; Yan WU ³ ; Chao PENG ⁵ ; Jun WANG ¹ ; Chenghao ZHU ¹ ; Xiuna YANG ¹ ; Kailin YANG ⁶ ; Ying LEI ¹ ; Luke W GUDDAT ⁷ ; Wenqing XU ¹ ; Gengfu XIAO ³ ; Lei SUN ⁸ ; Leike ZHANG ⁹ ; Zihe RAO ¹⁰ ; Haitao YANG ¹¹
Author Information

1. Shanghai Institute for Advanced Immunochemical Studies and School of Life Science and Technology, ShanghaiTech University, Shanghai, 201210, China.
2. Laboratory of Structural Biology, School of Life Sciences and School of Medicine, Tsinghua University, Beijing, 100091, China.
3. State Key Laboratory of Virology, Wuhan Institute of Virology, Center for Biosafety Mega-Science, Chinese Academy of Sciences, Wuhan, 430071, China.
4. The Fifth People's Hospital of Shanghai, Fudan University and Shanghai Key Laboratory of Medical Epigenetics, Institutes of Biomedical Sciences, Fudan University, Shanghai, 200032, China.
5. Zhangjiang Lab, National Facility for Protein Science in Shanghai, Shanghai Advanced Research Institute, Chinese Academy of Science, Shanghai, 201210, China.
6. Taussig Cancer Center, Cleveland Clinic, Cleveland, OH, 44195, USA.
7. School of Chemistry and Molecular Biosciences, The University of Queensland, Brisbane, Queensland, 4072, Australia.
8. The Fifth People's Hospital of Shanghai, Fudan University and Shanghai Key Laboratory of Medical Epigenetics, Institutes of Biomedical Sciences, Fudan University, Shanghai, 200032, China. llsun@fudan.edu.cn.
9. State Key Laboratory of Virology, Wuhan Institute of Virology, Center for Biosafety Mega-Science, Chinese Academy of Sciences, Wuhan, 430071, China. zhangleike@wh.iov.cn.
10. Shanghai Institute for Advanced Immunochemical Studies and School of Life Science and Technology, ShanghaiTech University, Shanghai, 201210, China. raozh@mail.tsinghua.edu.cn.
11. Shanghai Institute for Advanced Immunochemical Studies and School of Life Science and Technology, ShanghaiTech University, Shanghai, 201210, China. yanght@shanghaitech.edu.cn.
Publication Type:Research Support, Non-U.S. Gov't
Keywords: SARS-CoV-2; YM155; drug repurposing; interferon stimulating gene product 15; papain-like protease
MeSH: Antiviral Agents/therapeutic use*; Binding Sites; COVID-19/virology*; Coronavirus Papain-Like Proteases/metabolism*; Crystallography, X-Ray; Drug Evaluation, Preclinical; Drug Repositioning; High-Throughput Screening Assays/methods*; Humans; Imidazoles/therapeutic use*; Inhibitory Concentration 50; Molecular Dynamics Simulation; Mutagenesis, Site-Directed; Naphthoquinones/therapeutic use*; Protease Inhibitors/therapeutic use*; Protein Structure, Tertiary; Recombinant Proteins/isolation & purification*; SARS-CoV-2/isolation & purification*
From: Protein & Cell 2021;12(11):877-888
CountryChina
Language:English
Abstract: A new coronavirus (SARS-CoV-2) has been identified as the etiologic agent for the COVID-19 outbreak. Currently, effective treatment options remain very limited for this disease; therefore, there is an urgent need to identify new anti-COVID-19 agents. In this study, we screened over 6,000 compounds that included approved drugs, drug candidates in clinical trials, and pharmacologically active compounds to identify leads that target the SARS-CoV-2 papain-like protease (PLpro). Together with main protease (M