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 mu M, EC50 = 0.036 +/- 0.007 mu M). Thus, this study provides a useful quantitative structure-activity relationships model to develop potent inhibitors for enterovirus A71 3C protease.