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 I 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. (c) 2007 Elsevier Ltd. All rights reserved.