Premium
3D‐quantitative structure‐activity relationship study for the design of novel enterovirus A71 3C protease inhibitors
Author(s) -
Nie Quandeng,
Xu Xiaoyi,
Zhang Qi,
Ma Yuying,
Yin Zheng,
Shang Luqing
Publication year - 2018
Publication title -
chemical biology and drug design
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.59
H-Index - 77
eISSN - 1747-0285
pISSN - 1747-0277
DOI - 10.1111/cbdd.13344
Subject(s) - pharmacophore , protease , enterovirus , chemistry , enterovirus 71 , computational biology , structure–activity relationship , coxsackievirus , in vitro , biochemistry , enzyme , stereochemistry , biology , virology , virus
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 Auto GPA . 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 ( IC 50 = 0.031 ± 0.005 μM, EC 50 = 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.