title: Structure-based design, synthesis, and biological evaluation of peptidomimetic SARS-CoV 3CLpro inhibitors.
abstract: Structure-based design, synthesis, and biological evaluation of a series of peptidomimetic severe acute respiratory syndrome-coronavirus chymotrypsin-like protease inhibitors are described. These inhibitors were designed and synthesized based upon our X-ray crystal structure of inhibitor 1 bound to SARS-CoV 3CLpro. Incorporation of Boc-Ser as the P(4)-ligand resulted in enhanced SARS-CoV 3CLpro inhibitory activity. Structural analysis of the inhibitor-bound X-ray structure revealed high binding affinity toward the enzyme.
authors.affiliation: Departments of Chemistry and Medicinal Chemistry, Purdue University, West Lafayette, IN 47907, USA. akghosh@purdue.edu
authors.forename: Arun K
authors.initials: AK
authors.lastname: Ghosh
authors.forename: Kai
authors.initials: K
authors.lastname: Xi
authors.forename: Valerie
authors.initials: V
authors.lastname: Grum-Tokars
authors.forename: Xiaoming
authors.initials: X
authors.lastname: Xu
authors.forename: Kiira
authors.initials: K
authors.lastname: Ratia
authors.forename: Wentao
authors.initials: W
authors.lastname: Fu
authors.forename: Katherine V
authors.initials: KV
authors.lastname: Houser
authors.forename: Susan C
authors.initials: SC
authors.lastname: Baker
authors.forename: Michael E
authors.initials: ME
authors.lastname: Johnson
authors.forename: Andrew D
authors.initials: AD
authors.lastname: Mesecar
mesh_terms: D000086782:Coronavirus 3C Proteases; D018360:Crystallography, X-Ray; D003546:Cysteine Endopeptidases; D006860:Hydrogen Bonding; D008958:Models, Molecular; D018716:Molecular Mimicry; D015394:Molecular Structure; D011480:Protease Inhibitors / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D014764:Viral Proteins / Q000037:antagonists & inhibitors*
chemical_list: D011480:Protease Inhibitors; D014764:Viral Proteins; D003546:Cysteine Endopeptidases; D000086782:Coronavirus 3C Proteases