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DOI	10.1126/science.abb4489
	Structure-based design of antiviral drug candidates targeting the SARS-CoV-2 main protease
	Dai W.; Zhang B.; Jiang X.-M.; Su H.; Li J.; Zhao Y.; Xie X.; Jin Z.; Peng J.; Liu F.; Li C.; Li Y.; Bai F.; Wang H.; Cheng X.; Cen X.; Hu S.; Yang X.; Wang J.; Liu X.; Xiao G.; Jiang H.; Rao Z.; Zhang L.-K.; Xu Y.; Yang H.; Liu H.
发表日期	2020
ISSN	0036-8075
起始页码	1331
结束页码	1335
卷号	368 期号:6497
英文摘要	SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) is the etiological agent responsible for the global COVID-19 (coronavirus disease 2019) outbreak. The main protease of SARS-CoV-2, Mpro, is a key enzyme that plays a pivotal role in mediating viral replication and transcription. We designed and synthesized two lead compounds (11a and 11b) targeting Mpro. Both exhibited excellent inhibitory activity and potent anti-SARS-CoV-2 infection activity. The x-ray crystal structures of SARS-CoV-2 Mpro in complex with 11a or 11b, both determined at a resolution of 1.5 angstroms, showed that the aldehyde groups of 11a and 11b are covalently bound to cysteine 145 of Mpro. Both compounds showed good pharmacokinetic properties in vivo, and 11a also exhibited low toxicity, which suggests that these compounds are promising drug candidates. © 2020 American Association for the Advancement of Science. All rights reserved.
关键词	aldehyde antimicrobial activity drug enzyme activity infectivity inhibitor reaction kinetics viral disease Coronavirus SARS coronavirus 3C-like proteinase, Coronavirus antivirus agent cysteine proteinase viral protein animal Betacoronavirus chemical structure chemistry Chlorocebus aethiops Coronavirus infection dog drug design drug effect enzyme active site enzymology female human male mouse pandemic preclinical study protein tertiary structure Sprague Dawley rat toxicity testing Vero cell line virus pneumonia Animals Antiviral Agents Betacoronavirus Catalytic Domain Chlorocebus aethiops Coronavirus Infections Cysteine Endopeptidases Dogs Drug Design Drug Evaluation, Preclinical Female Humans Male Mice Molecular Structure Pandemics Pneumonia, Viral Protein Structure, Tertiary Rats, Sprague-Dawley Toxicity Tests Vero Cells Viral Nonstructural Proteins
语种	英语
来源机构	Science
文献类型	期刊论文
条目标识符	http://gcip.llas.ac.cn/handle/2XKMVOVA/133422
推荐引用方式 GB/T 7714	Dai W.,Zhang B.,Jiang X.-M.,et al. Structure-based design of antiviral drug candidates targeting the SARS-CoV-2 main protease[J]. Science,2020,368(6497).
APA	Dai W..,Zhang B..,Jiang X.-M..,Su H..,Li J..,...&Liu H..(2020).Structure-based design of antiviral drug candidates targeting the SARS-CoV-2 main protease.,368(6497).
MLA	Dai W.,et al."Structure-based design of antiviral drug candidates targeting the SARS-CoV-2 main protease".368.6497(2020).