title: Michael Acceptor-Based Peptidomimetic Inhibitor of Main Protease from Porcine Epidemic Diarrhea Virus.
abstract: Porcine epidemic diarrhea virus (PEDV) causes high mortality in pigs. PEDV main protease (Mpro) plays an essential role in viral replication. We solved the structure of PEDV Mprocomplexed with peptidomimetic inhibitor N3 carrying a Michael acceptor warhead, revealing atomic level interactions. We further designed a series of 17 inhibitors with altered side groups. Inhibitors M2 and M17 demonstrated enhanced specificity against PEDV Mpro. These compounds have potential as future therapeutics to combat PEDV infection.
authors.affiliation: School of Life Sciences, Tianjin University , Tianjin 300072, China.
authors.forename: Fenghua
authors.identifier: 0000-0002-4575-1858
authors.initials: F
authors.lastname: Wang
authors.affiliation: School of Life Sciences, Tianjin University , Tianjin 300072, China.|Tianjin International Joint Academy of Biotechnology and Medicine , Tianjin 300457, China.
authors.forename: Cheng
authors.identifier: 0000-0002-2228-2489
authors.initials: C
authors.lastname: Chen
authors.affiliation: Cleveland Clinic Lerner College of Medicine, Case Western Reserve University , Cleveland, Ohio 44195, United States.
authors.forename: Kailin
authors.identifier: 0000-0001-5968-6738
authors.initials: K
authors.lastname: Yang
authors.affiliation: Tianjin International Joint Academy of Biotechnology and Medicine , Tianjin 300457, China.
authors.forename: Yang
authors.identifier: 0000-0002-8786-1318
authors.initials: Y
authors.lastname: Xu
authors.affiliation: Tianjin International Joint Academy of Biotechnology and Medicine , Tianjin 300457, China.
authors.forename: Xiaomei
authors.identifier: 0000-0003-1060-8514
authors.initials: X
authors.lastname: Liu
authors.affiliation: Tianjin International Joint Academy of Biotechnology and Medicine , Tianjin 300457, China.
authors.forename: Fan
authors.identifier: 0000-0001-8207-6989
authors.initials: F
authors.lastname: Gao
authors.affiliation: Tianjin International Joint Academy of Biotechnology and Medicine , Tianjin 300457, China.
authors.forename: He
authors.identifier: 0000-0002-3936-9863
authors.initials: H
authors.lastname: Liu
authors.affiliation: School of Life Sciences, Tianjin University , Tianjin 300072, China.
authors.forename: Xia
authors.identifier: 0000-0001-6757-8534
authors.initials: X
authors.lastname: Chen
authors.affiliation: Department of Molecular Biophysics and Biochemistry, Yale University , New Haven, Connecticut 06520, United States.
authors.forename: Qi
authors.identifier: 0000-0002-3765-6025
authors.initials: Q
authors.lastname: Zhao
authors.affiliation: Tianjin International Joint Academy of Biotechnology and Medicine , Tianjin 300457, China.
authors.forename: Xiang
authors.identifier: 0000-0001-5498-6942
authors.initials: X
authors.lastname: Liu
authors.affiliation: Tianjin International Joint Academy of Biotechnology and Medicine , Tianjin 300457, China.
authors.forename: Yan
authors.identifier: 0000-0001-5915-4010
authors.initials: Y
authors.lastname: Cai
authors.affiliation: School of Life Sciences, Tianjin University , Tianjin 300072, China.|Tianjin International Joint Academy of Biotechnology and Medicine , Tianjin 300457, China.
authors.forename: Haitao
authors.identifier: 0000-0002-1875-3268
authors.initials: H
authors.lastname: Yang
mesh_terms: D000818:Animals; D018352:Coronavirus Infections / Q000188:drug therapy / Q000662:veterinary* / Q000821:virology; D062105:Molecular Docking Simulation; D010447:Peptide Hydrolases / Q000378:metabolism; D057786:Peptidomimetics / Q000737:chemistry / Q000494:pharmacology*; D053485:Porcine epidemic diarrhea virus / Q000187:drug effects / Q000201:enzymology*; D011480:Protease Inhibitors / Q000737:chemistry / Q000494:pharmacology*; D013552:Swine / Q000821:virology; D013553:Swine Diseases / Q000188:drug therapy* / Q000821:virology
chemical_list: D057786:Peptidomimetics; D011480:Protease Inhibitors; D010447:Peptide Hydrolases