Structure-activity relationship study of peptidomimetic aldehydes as enterovirus 71 3C protease inhibitors.

A series of peptidomimetic aldehydes were designed, synthesized, and evaluated for their biochemical activity against 3C protease (3Cpro) and anti-enterovirus 71 (EV71) activity in vitro. Molecular docking revealed that 5s (IC50 = 0.22 ± 0.07 μM, EC50 = 0.18 ± 0.05 μM) could bind well to the active site of EV71 3Cpro, which was consistent with the biological data compared to reference 5a (IC50 = 0.54 ± 0.02 μM, EC50 = 0.26 ± 0.07 μM). Structure and relationship study led to the discovery of aldehyde 5x (IC50 = 0.10 ± 0.02 μM, EC50 = 0.11 ± 0.07 μM), which exhibited the most potent 3Cpro inhibitory and antiviral activity.