Discovery of novel inhibitors of SARS-CoV-2 main protease

被引：2
|
作者：
Zheng, Lei [1 ]
Chen, Yanmei [1 ]
Bao, Jingxiao [1 ]
He, Liping [1 ]
Dong, Suzhen [1 ]
Qi, Yifei [1 ,2 ]
Zhang, John Z. H. [1 ,2 ,3 ,4 ]
机构：
[1] East China Normal Univ, Sch Chem & Mol Engn, Shanghai Key Lab Green Chem & Chem Proc, Shanghai Engn Res Ctr Mol Therapeut & New Drug De, Shanghai 200062, Peoples R China
[2] NYU Shanghai, NYUE CNU Ctr Computat Chem, Shanghai, Peoples R China
[3] NYU, Dept Chem, New York, NY USA
[4] Shanxi Univ, Collaborat Innovat Ctr Extreme Opt, Taiyuan, Shanxi, Peoples R China
来源：
JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS | 2022年 / 40卷 / 23期
基金：
中国国家自然科学基金; 上海市自然科学基金;
关键词：
COVID-19; main protease; inhibitory activity; virtual screening; INTERACTION ENTROPY; FREE-ENERGY; BINDING; SARS; ACCURACY; DOCKING;
D O I：
10.1080/07391102.2021.1972041
中图分类号：
Q5 [生物化学]; Q7 [分子生物学];
学科分类号：
071010 ; 081704 ;
摘要：
Corona Virus Disease 2019 (COVID-19), referred to as `New Coronary Pneumonia', is a type of acute infectious disease caused by the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection. M-pro is one of the main targets for treating COVID-19. The current research on M-pro mainly focuses on the repurposing of old drugs, and there are only a few novel ligands that inhibit M-pro. In this research, we used computational free energy calculation to screen a compound library against M-pro, and discovered four novel compounds with the two best compounds (AG-690/13507628 and AG-690/13507724) having experimental measured IC50 of just under 3 mu M and low cell toxicity. Detailed decomposition of the interactions between the inhibitors and M-pro reveals key interacting residues and interactions that determine the activity. The results from this study should provide a basis for further development of anti-SARS-CoV-2 drugs.
引用
收藏
页码：12526 / 12534
页数：9
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