南方科技大学知识苑(SUSTech KC): Development of potent and selective inhibitors targeting the papain-like protease of SARS-CoV-2

题名	Development of potent and selective inhibitors targeting the papain-like protease of SARS-CoV-2
作者	Shan，Hengyue 1,2; Liu，Jianping 3; Shen，Jiali 1,2; Dai，Jialin 1; Xu，Gang 4; Lu，Kuankuan 1,2; Han，Chao 1,2; Wang，Yaru 2,3; Xu，Xiaolong 2,3; Tong，Yilun 1,2; Xiang，Huaijiang 1; Ai，Zhiyuan 1; Zhuang，Guanglei 5; Hu，Junhao 1; Zhang，Zheng 4 ; Li，Ying 1; Pan，Lifeng 2,3; Tan，Li 1
通讯作者	Zhang，Zheng
发表日期	2021
DOI	10.1016/j.chembiol.2021.04.020
发表期刊	Cell Chemical Biology 影响因子和分区
ISSN	2451-9456
EISSN	2451-9448
摘要	The COVID-19 pandemic has been disastrous to society and effective drugs are urgently needed. The papain-like protease domain (PLpro) of SARS-CoV-2 (SCoV2) is indispensable for viral replication and represents a putative target for pharmacological intervention. In this work, we describe the development of a potent and selective SCoV2 PLpro inhibitor, 19. The inhibitor not only effectively blocks substrate cleavage and immunosuppressive function imparted by PLpro, but also markedly mitigates SCoV2 replication in human cells, with a submicromolar IC. We further present a convenient and sensitive activity probe, 7, and complementary assays to readily evaluate SCoV2 PLpro inhibitors in vitro or in cells. In addition, we disclose the co-crystal structure of SCoV2 PLpro in complex with a prototype inhibitor, which illuminates their detailed binding mode. Overall, these findings provide promising leads and important tools for drug discovery aiming to target SCoV2 PLpro.
关键词	assay development COVID-19 high-throughput screening lead optimization papain-like protease SARS-CoV-2 small-molecule inhibitor structure-based design
相关链接	[Scopus记录]
收录类别	SCI
语种	英语
学校署名	通讯
WOS记录号	WOS:000663304500013
Scopus记录号	2-s2.0-85105747513
来源库	Scopus
引用统计	被引频次[WOS]：57
成果类型	期刊论文
条目标识符	http://sustech.caswiz.com/handle/2SGJ60CL/228505
专题	南方科技大学医学院南方科技大学第二附属医院
作者单位	1.Interdisciplinary Research Center on Biology and Chemistry,Shanghai Institute of Organic Chemistry,Chinese Academy of Sciences,Shanghai,201210,China 2.University of Chinese Academy of Sciences,Beijing,100049,China 3.State Key Laboratory of Bioorganic and Natural Products Chemistry,Shanghai Institute of Organic Chemistry,Chinese Academy of Sciences,Shanghai,200032,China 4.Institute of Hepatology,National Clinical Research Center for Infectious Disease,Shenzhen Third People's Hospital,The Second Affiliated Hospital,School of Medicine,Southern University of Science and Technology,Shenzhen,518112,China 5.State Key Laboratory of Oncogenes and Related Genes,Shanghai Cancer Institute,Ren Ji Hospital,School of Medicine,Shanghai Jiao Tong University,Shanghai,200240,China
通讯作者单位	南方科技大学医学院; 南方科技大学第二附属医院
推荐引用方式 GB/T 7714	Shan，Hengyue,Liu，Jianping,Shen，Jiali,et al. Development of potent and selective inhibitors targeting the papain-like protease of SARS-CoV-2[J]. Cell Chemical Biology,2021.
APA	Shan，Hengyue.,Liu，Jianping.,Shen，Jiali.,Dai，Jialin.,Xu，Gang.,...&Tan，Li.(2021).Development of potent and selective inhibitors targeting the papain-like protease of SARS-CoV-2.Cell Chemical Biology.
MLA	Shan，Hengyue,et al."Development of potent and selective inhibitors targeting the papain-like protease of SARS-CoV-2".Cell Chemical Biology (2021).