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 Mpro complexed 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.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Coronavirus Infections / drug therapy
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Coronavirus Infections / veterinary*
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Coronavirus Infections / virology
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Molecular Docking Simulation
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Peptide Hydrolases / metabolism
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Peptidomimetics / chemistry
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Peptidomimetics / pharmacology*
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Porcine epidemic diarrhea virus / drug effects
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Porcine epidemic diarrhea virus / enzymology*
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Protease Inhibitors / chemistry
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Protease Inhibitors / pharmacology*
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Swine / virology
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Swine Diseases / drug therapy*
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Swine Diseases / virology
Substances
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Peptidomimetics
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Protease Inhibitors
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Peptide Hydrolases