title: Design, synthesis, and bioevaluation of viral 3C and 3C-like protease inhibitors.
abstract: A class of tripeptidyl transition state inhibitors containing a P1 glutamine surrogate, a P2 leucine, and a P3 arylalanines, was found to potently inhibit Norwalk virus replication in enzyme and cell based assays. An array of warheads, including aldehyde, α-ketoamide, bisulfite adduct, and α-hydroxyphosphonate transition state mimic, was also investigated. Tripeptidyls 2 and 6 possess antiviral activities against noroviruses, human rhinovirus, severe acute respiratory syndrome coronavirus, and coronavirus 229E, suggesting a broad range of antiviral activities.
authors.affiliation: Department of Chemistry, Kansas State University, 213 CBC Building, Manhattan, KS 66506, United States.
authors.forename: Allan M
authors.initials: AM
authors.lastname: Prior
authors.forename: Yunjeong
authors.initials: Y
authors.lastname: Kim
authors.forename: Sahani
authors.initials: S
authors.lastname: Weerasekara
authors.forename: Meghan
authors.initials: M
authors.lastname: Moroze
authors.forename: Kevin R
authors.initials: KR
authors.lastname: Alliston
authors.forename: Roxanne Adeline Z
authors.initials: RA
authors.lastname: Uy
authors.forename: William C
authors.initials: WC
authors.lastname: Groutas
authors.forename: Kyeong-Ok
authors.initials: KO
authors.lastname: Chang
authors.forename: Duy H
authors.initials: DH
authors.lastname: Hua
mesh_terms: D000998:Antiviral Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D000086782:Coronavirus 3C Proteases; D003546:Cysteine Endopeptidases / Q000737:chemistry / Q000378:metabolism*; D015195:Drug Design; D005973:Glutamine / Q000031:analogs & derivatives / Q000494:pharmacology; D006801:Humans; D008958:Models, Molecular; D011480:Protease Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship
chemical_list: D000998:Antiviral Agents; D011480:Protease Inhibitors; D005973:Glutamine; D003546:Cysteine Endopeptidases; D000086782:Coronavirus 3C Proteases
keywords: Coronavirus 229E; Human rhinovirus; Norovirus; Severe acute respiratory syndrome coronavirus; Viral 3C and 3C-like protease inhibitors