Molecular mechanism of ensitrelvir inhibiting SARS-CoV-2 main protease and its variants

doi:10.1038/s42003-023-05071-y

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	Molecular mechanism of ensitrelvir inhibiting SARS-CoV-2 main protease and its variants
	Lin, Mengmeng 1,2,3,4; Zeng, Xudong3,4 ; Duan, Yinkai3,4 ; Yang, Zinan3,4 ; Ma, Yuanyuan3,4 ; Yang, Haitao3,4 ; Yang, Xiuna3,4 ; Liu, Xiang 1
	2023-07-05
发表期刊	COMMUNICATIONS BIOLOGY (IF:5.2[JCR-2023],5.6[5-Year])
EISSN	2399-3642
卷号	6 期号:1
发表状态	已发表
DOI	10.1038/s42003-023-05071-y
摘要	["SARS-CoV-2 poses an unprecedented threat to the world as the causative agent of the COVID-19 pandemic. Among a handful of therapeutics developed for the prevention and treatment of SARS-CoV-2 infection, ensitrelvir is the first noncovalent and nonpeptide oral inhibitor targeting the main protease (M-pro) of SARS-CoV-2, which recently received emergency regulatory approval in Japan. Here we determined a 1.8-& ANGS; structure of M-pro in complex with ensitrelvir, which revealed that ensitrelvir targets the substrate-binding pocket of M-pro, specifically recognizing its S1, S2, and S1' subsites. Further, our comprehensive biochemical and structural data have demonstrated that even though ensitrelvir and nirmatrelvir (an FDA-approved drug) belong to different types of M-pro inhibitors, both of them remain to be effective against M(pro)s from all five SARS-CoV-2 variants of concern, suggesting M-pro is a bona fide broad-spectrum target. The molecular mechanisms uncovered in this study provide basis for future inhibitor design.","Structural and biochemical characterization of the SARS-CoV-2 main protease in complex with inhibitor ensitrelvir or nirmatrelvir reveals the mechanisms of inhibition."]
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收录类别	SCI
语种	英语
资助项目	Ramp;D Program of Guangzhou Laboratory["SRPG22-003","SRPG22-011"] ; Science and Technology Commission of Shanghai Municipality["YDZX20213100001556","20XD1422900"] ; Shanghai Municipal Science and Technology Major Project[ZD2021CY001] ; National Natural Science Foundation of China["92169109","32171259"]
WOS研究方向	Life Sciences & Biomedicine - Other Topics ; Science & Technology - Other Topics
WOS类目	Biology ; Multidisciplinary Sciences
WOS记录号	WOS:001024010100001
出版者	NATURE PORTFOLIO
引用统计	被引频次：26[WOS] [WOS记录] [WOS相关记录]
文献类型	期刊论文
条目标识符	https://kms.shanghaitech.edu.cn/handle/2MSLDSTB/321444
专题	免疫化学研究所生命科学与技术学院免疫化学研究所_特聘教授组_饶子和组生命科学与技术学院_硕士生生命科学与技术学院_博士生免疫化学研究所_PI研究组_杨海涛组
通讯作者	Yang, Xiuna; Liu, Xiang
作者单位	1.Nankai Univ, Coll Life Sci, State Key Lab Med Chem Biol, Tianjin, Peoples R China 2.Chongqing Med Univ, Inst Life Sci, Chongqing, Peoples R China 3.ShanghaiTech Univ, Shanghai Inst Adv Immunochem Studies, Shanghai, Peoples R China 4.ShanghaiTech Univ, Sch Life Sci & Technol, Shanghai, Peoples R China
第一作者单位	免疫化学研究所; 生命科学与技术学院
通讯作者单位	免疫化学研究所; 生命科学与技术学院
推荐引用方式 GB/T 7714	Lin, Mengmeng,Zeng, Xudong,Duan, Yinkai,et al. Molecular mechanism of ensitrelvir inhibiting SARS-CoV-2 main protease and its variants[J]. COMMUNICATIONS BIOLOGY,2023,6(1).
APA	Lin, Mengmeng.,Zeng, Xudong.,Duan, Yinkai.,Yang, Zinan.,Ma, Yuanyuan.,...&Liu, Xiang.(2023).Molecular mechanism of ensitrelvir inhibiting SARS-CoV-2 main protease and its variants.COMMUNICATIONS BIOLOGY,6(1).
MLA	Lin, Mengmeng,et al."Molecular mechanism of ensitrelvir inhibiting SARS-CoV-2 main protease and its variants".COMMUNICATIONS BIOLOGY 6.1(2023).