Novel nucleocapsid protein-targeting phenanthridine inhibitors of SARS-CoV-2

doi:10.1016/j.ejmech.2021.113966

KIB OpenIR

	Novel nucleocapsid protein-targeting phenanthridine inhibitors of SARS-CoV-2
	Wang,Yi-Ting ; Long,Xin-Yan ; Ding,Xiao ; Fan,Shi-Rui ; Cai,Jie-Yun ; Yang,Bi-Juan ; Zhang,Xin-Fang ; Luo,Rong-hua ; Yang,Lian ; Ruan,Ting ; Ren,Juan ; Jing,Chen-Xu ; Zheng,Yong-Tang ; Hao,Xiao-Jiang; Chen,Duo-Zhi
	2022
Source Publication	EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
ISSN	0223-5234
Volume	227 Pages:113966
Abstract	The COVID-19 pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is unprecedented in human history. As a major structural protein, nucleocapsid protein (NPro) is critical to the replication of SARS-CoV-2. In this work, 17 NPro-targeting phenanthridine derivatives were rationally designed and synthesized, based on the crystal structure of NPro. Most of these compounds can interact with SARS-CoV-2 NPro tightly and inhibit the replication of SARS-CoV-2 in vitro. Compounds 12 and 16 exhibited the most potent anti-viral activities with 50% effective concentration values of 3.69 and 2.18 mu M, respectively. Furthermore, site-directed mutagenesis of NPro and Surface Plasmon Resonance (SPR) assays revealed that 12 and 16 target N-terminal domain (NTD) of NPro by binding to Tyr109. This work found two potent anti-SARS-CoV-2 bioactive compounds and also indicated that SARS-CoV-2 NPro-NTD can be a target for new anti-virus agents. (C) 2021 Elsevier Masson SAS. All rights reserved.
Keyword	Phenanthridine Nucleocapsid protein SARS-CoV-2 N-terminal domain N-TERMINAL DOMAIN CORONAVIRUS
DOI	10.1016/j.ejmech.2021.113966
WOS ID	WOS:000744228500007
Citation statistics
Document Type	期刊论文
Identifier	http://ir.kib.ac.cn/handle/151853/73655
Collection	中国科学院昆明植物研究所
Affiliation	1.[Wang, Yi-Ting 2.Ding, Xiao 3.Fan, Shi-Rui 4.Cai, Jie-Yun 5.Yang, Bi-Juan 6.Zhang, Xin-Fang 7.Yang, Lian 8.Ruan, Ting 9.Ren, Juan 10.Jing, Chen-Xu 11.Hao, Xiao-Jiang 12.Chinese Acad Sci, Kunming Inst Bot, State Key Lab Phytochem & Plant Resources West Ch, Kunming 650201, Yunnan, Peoples R China 13.[Long, Xin-Yan 14.Luo, Rong-hua 15.Chinese Acad Sci, Key Lab Anim Models & Human Dis Mech, Key Lab Bioact Peptides Yunnan Prov, Kunming Inst Zool, Kunming 650223, Yunnan, Peoples R China 16.Univ Chinese Acad Sci, Kunming Coll Life Sci, Kunming 650204, Yunnan, Peoples R China 17.[Zhang, Xin-Fang 18.Yunnan Univ, Dept Chem Sci & Engn, Kunming 650091, Yunnan, Peoples R China
Recommended Citation GB/T 7714	Wang,Yi-Ting,Long,Xin-Yan,Ding,Xiao,et al. Novel nucleocapsid protein-targeting phenanthridine inhibitors of SARS-CoV-2[J]. EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY,2022,227:113966.
APA	Wang,Yi-Ting.,Long,Xin-Yan.,Ding,Xiao.,Fan,Shi-Rui.,Cai,Jie-Yun.,...&Chen,Duo-Zhi.(2022).Novel nucleocapsid protein-targeting phenanthridine inhibitors of SARS-CoV-2.EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY,227,113966.
MLA	Wang,Yi-Ting,et al."Novel nucleocapsid protein-targeting phenanthridine inhibitors of SARS-CoV-2".EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY 227(2022):113966.

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