Structure-based design of ketone-containing, tripeptidyl human rhinovirus 3C protease inhibitors

Tripeptide-derived molecules incorporating C-terminal ketone electrophiles were evaluated as reversible inhibitors of the cysteine-containing human rhinovirus 3C protease (3CP). An optimized example of such compounds displayed potent 3CP inhibition activity (K-i = 0.0045 mu M) and in vitro antiviral properties (EC50 = 0.34 mu M) when tested against HRV serotype-14. (C) 1999 Elsevier Science Ltd. All rights reserved.