Screening of electrophilic compounds yields an aziridinyl peptide as new active-site directed SARS-CoV main protease inhibitor.
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.
Martina
Erika
E
Institute of Pharmacy and Food Chemistry, University of Würzburg, Germany.
Stiefl
Nikolaus
N
Degel
Björn
B
Schulz
Franziska
F
Breuning
Alexander
A
Schiller
Markus
M
Vicik
Radim
R
Baumann
Knut
K
Ziebuhr
John
J
Schirmeister
Tanja
T
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
D001388:Aziridines; D010455:Peptides; D011480:Protease Inhibitors; D014764:Viral Proteins; D003546:Cysteine Endopeptidases; D000086782:Coronavirus 3C Proteases