Your browser doesn't support javascript.
Development of potent and selective inhibitors targeting the papain-like protease of SARS-CoV-2.
Shan, Hengyue; Liu, Jianping; Shen, Jiali; Dai, Jialin; Xu, Gang; Lu, Kuankuan; Han, Chao; Wang, Yaru; Xu, Xiaolong; Tong, Yilun; Xiang, Huaijiang; Ai, Zhiyuan; Zhuang, Guanglei; Hu, Junhao; Zhang, Zheng; Li, Ying; Pan, Lifeng; Tan, Li.
  • Shan H; Interdisciplinary Research Center on Biology and Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, Shanghai 201210, China; University of Chinese Academy of Sciences, Beijing 100049, China.
  • Liu J; State Key Laboratory of Bioorganic and Natural Products Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, Shanghai 200032, China.
  • Shen J; Interdisciplinary Research Center on Biology and Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, Shanghai 201210, China; University of Chinese Academy of Sciences, Beijing 100049, China.
  • Dai J; Interdisciplinary Research Center on Biology and Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, Shanghai 201210, China.
  • Xu G; 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, Guangdong Province 518112, China.
  • Lu K; Interdisciplinary Research Center on Biology and Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, Shanghai 201210, China; University of Chinese Academy of Sciences, Beijing 100049, China.
  • Han C; Interdisciplinary Research Center on Biology and Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, Shanghai 201210, China; University of Chinese Academy of Sciences, Beijing 100049, China.
  • Wang Y; University of Chinese Academy of Sciences, Beijing 100049, China; State Key Laboratory of Bioorganic and Natural Products Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, Shanghai 200032, China.
  • Xu X; University of Chinese Academy of Sciences, Beijing 100049, China; State Key Laboratory of Bioorganic and Natural Products Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, Shanghai 200032, China.
  • Tong Y; Interdisciplinary Research Center on Biology and Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, Shanghai 201210, China; University of Chinese Academy of Sciences, Beijing 100049, China.
  • Xiang H; Interdisciplinary Research Center on Biology and Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, Shanghai 201210, China.
  • Ai Z; Interdisciplinary Research Center on Biology and Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, Shanghai 201210, China.
  • Zhuang G; State Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200240, China.
  • Hu J; Interdisciplinary Research Center on Biology and Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, Shanghai 201210, China.
  • Zhang Z; 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, Guangdong Province 518112, China. Electronic address: zhangzheng1975@aliyu
  • Li Y; Interdisciplinary Research Center on Biology and Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, Shanghai 201210, China. Electronic address: liying@sioc.ac.cn.
  • Pan L; University of Chinese Academy of Sciences, Beijing 100049, China; State Key Laboratory of Bioorganic and Natural Products Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, Shanghai 200032, China. Electronic address: panlf@sioc.ac.cn.
  • Tan L; Interdisciplinary Research Center on Biology and Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, Shanghai 201210, China. Electronic address: tanli@sioc.ac.cn.
Cell Chem Biol ; 28(6): 855-865.e9, 2021 06 17.
Article in English | MEDLINE | ID: covidwho-1201399
ABSTRACT
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 IC50. 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.
Subject(s)
Keywords

Full text: Available Collection: International databases Database: MEDLINE Main subject: Protease Inhibitors / Drug Delivery Systems / Drug Development / Coronavirus Papain-Like Proteases / SARS-CoV-2 Type of study: Experimental Studies / Prognostic study Limits: Animals / Humans Language: English Journal: Cell Chem Biol Year: 2021 Document Type: Article Affiliation country: J.chembiol.2021.04.020

Similar

MEDLINE

...
LILACS

LIS


Full text: Available Collection: International databases Database: MEDLINE Main subject: Protease Inhibitors / Drug Delivery Systems / Drug Development / Coronavirus Papain-Like Proteases / SARS-CoV-2 Type of study: Experimental Studies / Prognostic study Limits: Animals / Humans Language: English Journal: Cell Chem Biol Year: 2021 Document Type: Article Affiliation country: J.chembiol.2021.04.020