Design, synthesis, and bioevaluation of viral 3C and 3C-like protease inhibitors

Click on the DOI link to access the article (may not be free).A class of tripeptidyl transition state inhibitors containing a P1 glutamine surrogate, a P2 leucine, and a P3 arylalanines, was found to potently inhibit Norwalk virus replication in enzyme and cell based assays. An array of warheads, including aldehyde, a-ketoamide, bisulfite adduct, and a-hydroxyphosphonate transition state mimic, was also investigated. Tripeptidyls 2 and 6 possess antiviral activities against noroviruses, human rhinovirus, severe acute respiratory syndrome coronavirus, and coronavirus 229E, suggesting a broad range of antiviral activities.NIH Grant U01AI081891. Moroze was funded through the ASSURE program of the Department of Defense in partnership with the NSF REU Site program number 1004991