title: Design and synthesis of peptidomimetic severe acute respiratory syndrome chymotrypsin-like protease inhibitors.
abstract: Design, synthesis, and biological evaluation of peptidomimetic severe acute respiratory syndrome chymotrypsin-like protease (SARS-3CLpro) inhibitors for severe acute respiratory syndrome coronavirus (SARS-CoV) are described. These inhibitors exhibited antiviral activity against SARS-CoV in infected cells in the micromolar range. An X-ray crystal structure of our lead inhibitor (4) bound to SARS-3CLpro provided important drug-design templates for the design of small-molecule inhibitors.
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: Kiira
authors.initials: K
authors.lastname: Ratia
authors.forename: Bernard D
authors.initials: BD
authors.lastname: Santarsiero
authors.forename: Wentao
authors.initials: W
authors.lastname: Fu
authors.forename: Brian H
authors.initials: BH
authors.lastname: Harcourt
authors.forename: Paul A
authors.initials: PA
authors.lastname: Rota
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: D000818:Animals; D000998:Antiviral Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D002478:Cells, Cultured; D053818:Chymases; D018360:Crystallography, X-Ray; D004151:Dipeptides / Q000737:chemistry; D015195:Drug Design; D006801:Humans; D007555:Isoxazoles / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D007700:Kinetics; D007769:Lactams / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D008958:Models, Molecular; D018716:Molecular Mimicry; D010455:Peptides / Q000737:chemistry*; D045473:Severe acute respiratory syndrome-related coronavirus / Q000187:drug effects / Q000201:enzymology*; D012697:Serine Endopeptidases / Q000737:chemistry / Q000378:metabolism*; D015842:Serine Proteinase Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D013237:Stereoisomerism; D013329:Structure-Activity Relationship
chemical_list: D000998:Antiviral Agents; D004151:Dipeptides; D007555:Isoxazoles; D007769:Lactams; D010455:Peptides; D015842:Serine Proteinase Inhibitors; D012697:Serine Endopeptidases; D053818:Chymases