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Characterization and noncovalent inhibition of the K63-deubiquitinase activity of SARS-cov-2 PLpro

文献类型：期刊论文

作者Liu, Xin7; Zheng, Miao5,7; Zhang, Hongqing6; Feng, Bo5,7; Li, Jiaqi6; Zhang, Yanan6; Zhang, Ji6; Zhao, Na5,7; Li, Chaoqiang7; Song, Ning7
刊名ANTIVIRAL RESEARCH
出版日期2024-08-01
卷号228页码:12
ISSN号0166-3542
DOI10.1016/j.antiviral.2024.105944
通讯作者Li, Jia() ; Zhang, Bo() ; Zhou, Yu() ; Zheng, Jie(jiezheng@shsmu.edu.cn)
英文摘要SARS-CoV-2 papain-like protease (PLpro) could facilitate viral replication and host immune evasion by respectively hydrolyzing viral polyprotein and host ubiquitin conjugates, thereby rendering itself as an important antiviral target. Yet few noncovalent PLpro inhibitors of SARS-CoV-2 have been reported with improved directed towards pathogenic deubiquitinating activities inhibition. Herein, we report that coronavirus PLpro proteases have distinctive substrate bias and are conserved to deubiquitylate K63 -linked polyubiquitination, thereby attenuating host type I interferon response. We identify a noncovalent compound specifically optimized towards halting the K63-deubiquitinase activity of SARS-CoV-2 PLpro, but not other coronavirus (CoV) counterparts or host deubiquitinase. Contrasting with GRL0617, a SARS-CoV-1 PLpro inhibitor, SIMM-036 is 50 -fold and 7 -fold (half maximal inhibitory concentration (IC 50 )) more potent to inhibit viral replication during SARS-CoV-2 infection and restore the host interferon- beta (IFN- beta) response in human angiotensin-converting enzyme 2 (hACE2)-HeLa cells, respectively. Structureactivity relationship (SAR) analysis further reveals the importance of BL2 groove of PLpro, which could determine the selectivity of K63-deubiquitinase activity of the enzyme.
WOS关键词PAPAIN-LIKE PROTEASE ; RESPIRATORY SYNDROME CORONAVIRUS ; NF-KAPPA-B ; RIG-I ; ADAPTER PROTEIN ; INNATE ; DEUBIQUITINASE ; IDENTIFICATION ; PATHWAY ; DOMAIN
资助项目National Natural Science Foundation of China[81971538] ; National Natural Science Foundation of China[32222048] ; National Natural Science Foundation of China[82151219] ; National Natural Science Foundation of China[82130105] ; Strategic Priority Research Program of Chinese Academy of Sciences[SIMM010109] ; Strategic Priority Research Program of Chinese Academy of Sciences[SIMM010111] ; Creative Research Group Program of Natural Science Foundation of Hubei Province[2022CFA021]
WOS研究方向Pharmacology & Pharmacy ; Virology
语种英语
WOS记录号WOS:001264408400001
出版者ELSEVIER
源URL[http://119.78.100.183/handle/2S10ELR8/313089]  
专题中国科学院上海药物研究所
通讯作者Li, Jia; Zhang, Bo; Zhou, Yu; Zheng, Jie
作者单位1.Shanghai Jiao Tong Univ, Shanghai Inst Virol, Sch Med, Shanghai 200025, Peoples R China
2.Univ Chinese Acad Sci, Beijing 100049, Peoples R China
3.UCAS, Hangzhou Inst Adv Study, Sch Pharmaceut Sci & Technol, Hangzhou 310024, Peoples R China
4.Nanjing Univ Chinese Med, Sch Chinese Mat Med, Nanjing 210023, Jiangsu, Peoples R China
5.Shenyang Pharmaceut Univ, Shenyang 110016, Peoples R China
6.Chinese Acad Sci, Wuhan Inst Virol, Ctr Biosafety Mega Sci, Key Lab Special Pathogens & Biosafety, Wuhan, Peoples R China
7.Chinese Acad Sci, Shanghai Inst Mat Med, Shanghai 201203, Peoples R China
推荐引用方式
GB/T 7714		 Liu, Xin,Zheng, Miao,Zhang, Hongqing,et al. Characterization and noncovalent inhibition of the K63-deubiquitinase activity of SARS-cov-2 PLpro[J]. ANTIVIRAL RESEARCH,2024,228:12.
APA Liu, Xin.,Zheng, Miao.,Zhang, Hongqing.,Feng, Bo.,Li, Jiaqi.,...&Zheng, Jie.(2024).Characterization and noncovalent inhibition of the K63-deubiquitinase activity of SARS-cov-2 PLpro.ANTIVIRAL RESEARCH,228,12.
MLA Liu, Xin,et al."Characterization and noncovalent inhibition of the K63-deubiquitinase activity of SARS-cov-2 PLpro".ANTIVIRAL RESEARCH 228(2024):12.

入库方式： OAI收割

来源：上海药物研究所

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