High-throughput screening of SARS-CoV-2 main and papain-like protease inhibitors

doi:10.1093/procel/pwac016

	High-throughput screening of SARS-CoV-2 main and papain-like protease inhibitors
	Zang, Yi 1,2,3,4; Su, Mingbo 5; Wang, Qingxing 6,7; Cheng, Xi 2,3,4; Zhang, Wenru 5; Zhao, Yao8,9 ; Chen, Tong 2,3,6; Jiang, Yingyan 1; Shen, Qiang 1; Du, Juan 4; Tan, Qiuxiang 2,3; Wang, Peipei 1,2,3; Gao, Lixin 1,2,3; Jin, Zhenming 8,9; Zhang, Mengmeng 1,2,3; Li, Cong 1,2,3; Zhu, Ya 2,3; Feng, Bo 1,2,3; Tang, Bixi 1,2,3; Xie, Han 2,3; Wang, Ming-Wei 1,2,3,6; Zheng, Mingyue 2,3,4,6; Pan, Xiaoyan 7; Yang, Haitao8,9 ; Xu, Yechun 2,3,4,6; Wu, Beili 2,3,4,6,10; Zhang, Leike 7; Rao, Zihe8,9 ; Yang, Xiuna8,9 ; Jiang, Hualiang 2,3,4,6; Xiao, Gengfu 7; Zhao, Qiang 2,3,4,10,11; Li, Jia 1,2,3,4,5,11
	2023-01-20
发表期刊	PROTEIN & CELL (IF:13.6[JCR-2023],17.7[5-Year])
ISSN	1674-800X
EISSN	1674-8018
卷号	14 期号:1
发表状态	已发表
DOI	10.1093/procel/pwac016
摘要	The global COVID-19 coronavirus pandemic has infected over 109 million people, leading to over 2 million deaths up to date and still lacking of effective drugs for patient treatment. Here, we screened about 1.8 million small molecules against the main protease (M-pro) and papain like protease (PLpro), two major proteases in severe acute respiratory syndrome-coronavirus 2 genome, and identified 1851M(pro) inhibitors and 205 PLpro inhibitors with low nmol/l activity of the best hits. Among these inhibitors, eight small molecules showed dual inhibition effects on both M-pro and PLpro, exhibiting potential as better candidates for COVID-19 treatment. The best inhibitors of each protease were tested in antiviral assay, with over 40% of M-pro inhibitors and over 20% of PLpro inhibitors showing high potency in viral inhibition with low cytotoxicity. The X-ray crystal structure of SARS-CoV-2 M-pro in complex with its potent inhibitor 4a was determined at 1.8 angstrom resolution. Together with docking assays, our results provide a comprehensive resource for future research on anti-SARS-CoV-2 drug development.
关键词	high-throughput screening SARS CoV-2 main papain-like proteases
URL	查看原文
收录类别	SCI ; SCOPUS
语种	英语
资助项目	National Key R&D Program of China["2018YFA0507000","2018ZX09735001","2020YFC0844500"] ; National Science Foundation of China["31825010","81525024","81673489"] ; Key Research Program of Frontier Sciences, CAS["QYZDB-SSW-SMC024","QYZDB-SSW-SMC054"] ; Fund of Chinese Academy of Sciences[2020YJFK0105] ; Chinese Academy of Engineering[2020-CMKYGG-05] ; Jack Ma Foundation[2020-CMKYGG-05] ; Shanghai Science and Technology Development Funds[20431900200] ; Fund of Youth Innovation Promotion Association[2018319] ; Hubei Science and Technology Project[2020FCA003] ; Fund of Chinese Academy of Sciences[2020YJFK0105]
WOS研究方向	Cell Biology
WOS类目	Cell Biology
WOS记录号	WOS:000923531200003
出版者	OXFORD UNIV PRESS
引用统计	正在获取...
文献类型	期刊论文
条目标识符	https://kms.shanghaitech.edu.cn/handle/2MSLDSTB/282121
专题	免疫化学研究所_特聘教授组_饶子和组生命科学与技术学院免疫化学研究所_PI研究组_杨海涛组
通讯作者	Yang, Xiuna; Jiang, Hualiang; Xiao, Gengfu; Zhao, Qiang; Li, Jia
作者单位	1.Chinese Acad Sci, Shanghai Inst Mat Med, Natl Ctr Drug Screening, Shanghai 201203, Peoples R China 2.Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, Shanghai 201203, Peoples R China 3.Chinese Acad Sci, Shanghai Inst Mat Med, CAS Key Lab Receptor Res, Shanghai 201203, Peoples R China 4.UCAS, Hangzhou Inst Adv Study, Sch Pharmaceut Sci & Technol, Hangzhou 310024, Peoples R China 5.Nanjing Univ Chinese Med, Sch Chinese Mat Med, Nanjing 210023, Peoples R China 6.Univ Chinese Acad Sci, Beijing 100049, Peoples R China 7.Chinese Acad Sci, Wuhan Inst Virol, Ctr Biosafety Mega Sci, State Key Lab Virol, Wuhan 430071, Peoples R China 8.ShanghaiTech Univ, Shanghai Inst Adv Immunochem Studies, Shanghai 201210, Peoples R China 9.ShanghaiTech Univ, Sch Life Sci & Technol, Shanghai 201210, Peoples R China 10.Chinese Acad Sci, CAS Ctr Excellence Biomacromolecules, Beijing 100101, Peoples R China 11.Chinese Acad Sci, Inst Drug Discovery & Dev, Zhongshan Branch, Beijing 528400, Guangdong, Peoples R China
通讯作者单位	免疫化学研究所; 生命科学与技术学院
推荐引用方式 GB/T 7714	Zang, Yi,Su, Mingbo,Wang, Qingxing,et al. High-throughput screening of SARS-CoV-2 main and papain-like protease inhibitors[J]. PROTEIN & CELL,2023,14(1).
APA	Zang, Yi.,Su, Mingbo.,Wang, Qingxing.,Cheng, Xi.,Zhang, Wenru.,...&Li, Jia.(2023).High-throughput screening of SARS-CoV-2 main and papain-like protease inhibitors.PROTEIN & CELL,14(1).
MLA	Zang, Yi,et al."High-throughput screening of SARS-CoV-2 main and papain-like protease inhibitors".PROTEIN & CELL 14.1(2023).