title: Screening of electrophilic compounds yields an aziridinyl peptide as new active-site directed SARS-CoV main protease inhibitor.
abstract: The coronavirus main protease, M(pro), is considered a major target for drugs suitable to combat coronavirus infections including the severe acute respiratory syndrome (SARS). In this study, comprehensive HPLC- and FRET-substrate-based screenings of various electrophilic compounds were performed to identify potential M(pro) inhibitors. The data revealed that the coronaviral main protease is inhibited by aziridine- and oxirane-2-carboxylates. Among the trans-configured aziridine-2,3-dicarboxylates the Gly-Gly-containing peptide 2c was found to be the most potent inhibitor.
authors.affiliation: Institute of Pharmacy and Food Chemistry, University of Würzburg, Germany.
authors.forename: Erika
authors.initials: E
authors.lastname: Martina
authors.forename: Nikolaus
authors.initials: N
authors.lastname: Stiefl
authors.forename: Björn
authors.initials: B
authors.lastname: Degel
authors.forename: Franziska
authors.initials: F
authors.lastname: Schulz
authors.forename: Alexander
authors.initials: A
authors.lastname: Breuning
authors.forename: Markus
authors.initials: M
authors.lastname: Schiller
authors.forename: Radim
authors.initials: R
authors.lastname: Vicik
authors.forename: Knut
authors.initials: K
authors.lastname: Baumann
authors.forename: John
authors.initials: J
authors.lastname: Ziebuhr
authors.forename: Tanja
authors.initials: T
authors.lastname: Schirmeister
mesh_terms: D001388:Aziridines / Q000494:pharmacology*; D001665:Binding Sites; D000086782:Coronavirus 3C Proteases; D003546:Cysteine Endopeptidases / Q000378:metabolism; D006801:Humans; D010455:Peptides / Q000494:pharmacology*; D011480:Protease Inhibitors / Q000494:pharmacology*; D045473:Severe acute respiratory syndrome-related coronavirus / Q000187:drug effects; D045169:Severe Acute Respiratory Syndrome / Q000188:drug therapy*; D014764:Viral Proteins / Q000378:metabolism
chemical_list: D001388:Aziridines; D010455:Peptides; D011480:Protease Inhibitors; D014764:Viral Proteins; D003546:Cysteine Endopeptidases; D000086782:Coronavirus 3C Proteases