The Structure of the Porcine Deltacoronavirus Main Protease Reveals a Conserved Target for the Design of Antivirals

doi:10.3390/v14030486

	The Structure of the Porcine Deltacoronavirus Main Protease Reveals a Conserved Target for the Design of Antivirals
	Wang, Fenghua 1,2,3; Chen, Cheng 1,2; Wang, Zefang 1,2; Han, Xu 1; Shi, Peidian 1; Zhou, Kaixuan 2; Liu, Xiaomei 2; Xiao, Yunjie 1; Cai, Yan 2; Huang, Jinhai 1; Zhang, Lei 1; Yang, Haitao1,2,4,5
	2022-03
发表期刊	VIRUSES-BASEL
EISSN	1999-4915
卷号	14 期号:3
发表状态	已发表
DOI	10.3390/v14030486
摘要	The existing zoonotic coronaviruses (CoVs) and viral genetic variants are important microbiological pathogens that cause severe disease in humans and animals. Currently, no effective broad-spectrum antiviral drugs against existing and emerging CoVs are available. The CoV main protease (M-pro) plays an essential role in viral replication, making it an ideal target for drug development. However, the structure of the Deltacoronavirus M-pro is still unavailable. Porcine deltacoronavirus (PDCoV) is a novel CoV that belongs to the genus Deltacoronavirus and causes atrophic enteritis, severe diarrhea, vomiting and dehydration in pigs. Here, we determined the structure of PDCoV M-pro complexed with a Michael acceptor inhibitor. Structural comparison showed that the backbone of PDCoV M-pro is similar to those of alpha-, beta- and gamma-CoV M(pro)s. The substrate-binding pocket of M-pro is well conserved in the subfamily Coronavirinae. In addition, we also observed that M(pro)s from the same genus adopted a similar conformation. Furthermore, the structure of PDCoV M-pro in complex with a Michael acceptor inhibitor revealed the mechanism of its inhibition of PDCoV M-pro. Our results provide a basis for the development of broad-spectrum antivirals against PDCoV and other CoVs.
关键词	coronaviruses porcine deltacoronavirus main protease broad-spectrum antivirals
URL	查看原文
收录类别	SCI ; SCIE
语种	英语
资助项目	Lingang Laboratory[LG202101-01-07] ; National Key R&D Program of China[2020YFA0707502] ; Science and Technology Commission of Shanghai Municipality["YDZX20213100001556","20XD1422900"] ; National Natural Science Foundation of China[92169109]
WOS研究方向	Virology
WOS类目	Virology
WOS记录号	WOS:000774646800001
出版者	MDPI
引用统计
文献类型	期刊论文
条目标识符	https://kms.shanghaitech.edu.cn/handle/2MSLDSTB/171475
专题	生命科学与技术学院免疫化学研究所_PI研究组_杨海涛组
通讯作者	Zhang, Lei; Yang, Haitao
作者单位	1.Tianjin Univ, Sch Life Sci, Tianjin 300072, Peoples R China 2.Tianjin Int Joint Acad Biotechnol & Med, Tianjin 300457, Peoples R China 3.Tianjin Univ Sci & Technol, Coll Biotechnol, Key Lab Ind Fermentat Microbiol, Tianjin Key Lab Ind Microbiol,Minist Educ, Tianjin 300457, Peoples R China 4.Shanghai Tech Univ, Shanghai Inst Adv Immunochem Studies, Shanghai 201210, Peoples R China 5.Shanghai Tech Univ, Sch Life Sci & Technol, Shanghai 201210, Peoples R China
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	Wang, Fenghua,Chen, Cheng,Wang, Zefang,et al. The Structure of the Porcine Deltacoronavirus Main Protease Reveals a Conserved Target for the Design of Antivirals[J]. VIRUSES-BASEL,2022,14(3).
APA	Wang, Fenghua.,Chen, Cheng.,Wang, Zefang.,Han, Xu.,Shi, Peidian.,...&Yang, Haitao.(2022).The Structure of the Porcine Deltacoronavirus Main Protease Reveals a Conserved Target for the Design of Antivirals.VIRUSES-BASEL,14(3).
MLA	Wang, Fenghua,et al."The Structure of the Porcine Deltacoronavirus Main Protease Reveals a Conserved Target for the Design of Antivirals".VIRUSES-BASEL 14.3(2022).