title: Isatin compounds as noncovalent SARS coronavirus 3C-like protease inhibitors.
abstract: A series of isatin derivatives were synthesized and tested against SARS CoV 3C-like protease. Substitutions at the N-1 and C-5 positions were examined to elucidate the differences in substrate binding sites of the rhinovirus 3C protease and SARS CoV 3C-like protease. Compound 5f shows significant inhibition with an IC(50) of 0.37 microM. Further study showed that, unlike the irreversible covalent binding of isatin derivatives to human rhinovirus 3C protease, the compounds tested in this study are all noncovalent reversible inhibitors.
authors.affiliation: State Key Laboratory for Structural Chemistry of Unstable and Stable Species, College of Chemistry and Molecular Engineering, Peking University, Beijing 100871, China.
authors.forename: Lu
authors.initials: L
authors.lastname: Zhou
authors.forename: Ying
authors.initials: Y
authors.lastname: Liu
authors.forename: Weilin
authors.initials: W
authors.lastname: Zhang
authors.forename: Ping
authors.initials: P
authors.lastname: Wei
authors.forename: Changkang
authors.initials: C
authors.lastname: Huang
authors.forename: Jianfeng
authors.initials: J
authors.lastname: Pei
authors.forename: Yaxia
authors.initials: Y
authors.lastname: Yuan
authors.forename: Luhua
authors.initials: L
authors.lastname: Lai
mesh_terms: D000086782:Coronavirus 3C Proteases; D003546:Cysteine Endopeptidases / Q000737:chemistry; D006801:Humans; D007510:Isatin / Q000031:analogs & derivatives* / Q000138:chemical synthesis* / Q000737:chemistry; D008958:Models, Molecular; D045473:Severe acute respiratory syndrome-related coronavirus / Q000201:enzymology*; D014764:Viral Proteins / Q000037:antagonists & inhibitors* / Q000737:chemistry
chemical_list: D014764:Viral Proteins; D007510:Isatin; D003546:Cysteine Endopeptidases; D000086782:Coronavirus 3C Proteases