Structure-based design of antiviral drug candidates targeting the SARS-CoV-2 main protease

doi:10.1126/science.abb4489

GSTDTAP > 气候变化

DOI	10.1126/science.abb4489
	Structure-based design of antiviral drug candidates targeting the SARS-CoV-2 main protease
	Wenhao Dai; Bing Zhang; Xia-Ming Jiang; Haixia Su; Jian Li; Yao Zhao; Xiong Xie; Zhenming Jin; Jingjing Peng; Fengjiang Liu; Chunpu Li; You Li; Fang Bai; Haofeng Wang; Xi Cheng; Xiaobo Cen; Shulei Hu; Xiuna Yang; Jiang Wang; Xiang Liu; Gengfu Xiao; Hualiang Jiang; Zihe Rao; Lei-Ke Zhang; Yechun Xu; Haitao Yang; Hong Liu
	2020-06-19
发表期刊	Science
出版年	2020
英文摘要	With no vaccine or proven effective drug against the virus that causes coronavirus disease 2019 (COVID-19), scientists are racing to find clinical antiviral treatments. A promising drug target is the viral main protease Mpro, which plays a key role in viral replication and transcription. Dai et al. designed two inhibitors, 11a and 11b, based on analyzing the structure of the Mpro active site. Both strongly inhibited the activity of Mpro and showed good antiviral activity in cell culture. Compound 11a had better pharmacokinetic properties and low toxicity when tested in mice and dogs, suggesting that this compound is a promising drug candidate. Science , this issue p. [1331][1] 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. [1]: /lookup/doi/10.1126/science.abb4489
领域	气候变化 ; 资源环境
URL	查看原文
引用统计	被引频次：980[WOS] [WOS记录] [WOS相关记录]
文献类型	期刊论文
条目标识符	http://119.78.100.173/C666/handle/2XK7JSWQ/276691
专题	气候变化资源环境科学
推荐引用方式 GB/T 7714	Wenhao Dai,Bing Zhang,Xia-Ming Jiang,et al. Structure-based design of antiviral drug candidates targeting the SARS-CoV-2 main protease[J]. Science,2020.
APA	Wenhao Dai.,Bing Zhang.,Xia-Ming Jiang.,Haixia Su.,Jian Li.,...&Hong Liu.(2020).Structure-based design of antiviral drug candidates targeting the SARS-CoV-2 main protease.Science.
MLA	Wenhao Dai,et al."Structure-based design of antiviral drug candidates targeting the SARS-CoV-2 main protease".Science (2020).