Structure-Based Virtual Screening and Identification of Potential Inhibitors of SARS-CoV-2 S-RBD and ACE2 Interaction

doi:10.3389/fchem.2021.740702

	Structure-Based Virtual Screening and Identification of Potential Inhibitors of SARS-CoV-2 S-RBD and ACE2 Interaction
	Xiong, Jiacheng 1,2; Xiang, Yusen 3; Huang, Ziming 1,2; Liu, Xiaohong 1,2,4; Wang, Mengge 3; Ge, Guangbo 3; Chen, Hongzhuan 3; Xu, Jianrong 5,6; Zheng, Mingyue 1,2; Chen, Lili 3
刊名	FRONTIERS IN CHEMISTRY
	2021-09-27
卷号	9 页码:12
关键词	SARS-CoV-2 angiotensin-converting enzyme 2 (ACE2) spike protein receptor-binding domain (S-RBD) structure-based virtual screening protein-protein interaction (PPI) inhibitors
ISSN号	2296-2646
DOI	10.3389/fchem.2021.740702
通讯作者	Xu, Jianrong(janker.xu@gmail.com) ; Zheng, Mingyue(myzheng@simm.ac.cn) ; Chen, Lili(llchen@shutcm.edu.cn)
英文摘要	The emergence and rapid spread of SARS-CoV-2 have caused a worldwide public health crisis. Designing small molecule inhibitors targeting SARS-CoV-2 S-RBD/ACE2 interaction is considered as a potential strategy for the prevention and treatment of SARS-CoV-2. But to date, only a few compounds have been reported as SARS-CoV-2 S-RBD/ACE2 interaction inhibitors. In this study, we described the virtual screening and experimental validation of two novel inhibitors (DC-RA016 and DC-RA052) against SARS-CoV-2 S-RBD/ACE2 interaction. The NanoBiT assays and surface plasmon resonance (SPR) assays demonstrated their capabilities of blocking SARS-CoV-2 S-RBD/ACE2 interaction and directly binding to both S-RBD and ACE2. Moreover, the pseudovirus assay revealed that these two compounds possessed significant antiviral activity (about 50% inhibition rate at maximum non-cytotoxic concentration). These results indicate that the compounds DC-RA016 and DC-RA052 are promising inhibitors against SARS-CoV-2 S-RBD/ACE2 interaction and deserve to be further developed.
资助项目	Scientific Research Project of Shanghai Municipal Health Commission on Traditional Chinese Medicine for Prevention and Treatment of COVID-19[2020XGKY07] ; Emergency Scientific Research Program of Shanghai University of Traditional Chinese Medicine[2019YJ 06-01] ; National Natural Science Foundation of China[81773634] ; Tencent AI Lab Rhino-Bird Focused Research Program[JR202002] ; Shanghai Science and Technology Innovation Action Plans - Shanghai Science and Technology Committee[20S21901500] ; Shanghai Science and Technology Innovation Action Plans - Shanghai Science and Technology Committee[20S21900900]
WOS关键词	RECEPTOR ; BINDING
WOS研究方向	Chemistry
语种	英语
出版者	FRONTIERS MEDIA SA
WOS记录号	WOS:000705528500001
内容类型	期刊论文
源URL	[http://119.78.100.183/handle/2S10ELR8/298451]
专题	中国科学院上海药物研究所
通讯作者	Xu, Jianrong; Zheng, Mingyue; Chen, Lili
作者单位	1.Chinese Acad Sci, Shanghai Inst Mat Med, Drug Discovery & Design Ctr, State Key Lab Drug Res, Shanghai, Peoples R China 2.Univ Chinese Acad Sci, Coll Pharm, Beijing, Peoples R China 3.Shanghai Univ Tradit Chinese Med, Inst Interdisciplinary Integrat Med Res, Shanghai, Peoples R China 4.ShanghaiTech Univ, Sch Life Sci & Technol, Shanghai Inst Adv Immunochem Studies, Shanghai, Peoples R China 5.Shanghai Univ Tradit Chinese Med, Acad Integrat Med, Shanghai, Peoples R China 6.Shanghai Jiao Tong Univ, Sch Med, Dept Pharmacol & Chem Biol, Shanghai, Peoples R China
推荐引用方式 GB/T 7714	Xiong, Jiacheng,Xiang, Yusen,Huang, Ziming,et al. Structure-Based Virtual Screening and Identification of Potential Inhibitors of SARS-CoV-2 S-RBD and ACE2 Interaction[J]. FRONTIERS IN CHEMISTRY,2021,9:12.
APA	Xiong, Jiacheng.,Xiang, Yusen.,Huang, Ziming.,Liu, Xiaohong.,Wang, Mengge.,...&Chen, Lili.(2021).Structure-Based Virtual Screening and Identification of Potential Inhibitors of SARS-CoV-2 S-RBD and ACE2 Interaction.FRONTIERS IN CHEMISTRY,9,12.
MLA	Xiong, Jiacheng,et al."Structure-Based Virtual Screening and Identification of Potential Inhibitors of SARS-CoV-2 S-RBD and ACE2 Interaction".FRONTIERS IN CHEMISTRY 9(2021):12.