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 P4-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.

Graphical abstractStructure-based design, synthesis, and biological evaluation of a series of peptidomimetic SARS-CoV 3CLpro inhibitors are described. Inhibitor 3-bound SAR-3CLpro X-ray crystal structure provided molecular insight into the ligand-binding site interactions.Figure optionsDownload full-size imageDownload as PowerPoint slide