Structure-based design, synthesis, and biological evaluation of peptidomimetic SARS-CoV 3CLpro inhibitors.
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.
Ghosh
Arun K
AK
Departments of Chemistry and Medicinal Chemistry, Purdue University, West Lafayette, IN 47907, USA. akghosh@purdue.edu
Xi
Kai
K
Grum-Tokars
Valerie
V
Xu
Xiaoming
X
Ratia
Kiira
K
Fu
Wentao
W
Houser
Katherine V
KV
Baker
Susan C
SC
Johnson
Michael E
ME
Mesecar
Andrew D
AD
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*
D011480:Protease Inhibitors; D014764:Viral Proteins; D003546:Cysteine Endopeptidases; D000086782:Coronavirus 3C Proteases