3D-Quantitative Structure-Activity Relationship Study for the Design of Novel Enterovirus A71 3C Protease Inhibitors

A three‐dimensional quantitative structure‐activity relationships model of enterovirus A71 3C protease inhibitors was constructed in this study. The protein‐ligand interaction fingerprint was analyzed to generate a pharmacophore model. A predictive and reliable three‐dimensional quantitative structure‐activity relationships model was built based on the Flexible Alignment of AutoGPA. Moreover, three novel compounds (I–III) were designed and evaluated for their biochemical activity against 3C protease and anti‐enterovirus A71 activity in vitro. III exhibited excellent inhibitory activity (IC50 = 0.031 ± 0.005 μM, EC50 = 0.036 ± 0.007 μM). Thus, this study provides a useful quantitative structure‐activity relationships model to develop potent inhibitors for enterovirus A71 3C protease.