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In vitro Antiviral Effects and 3 D QSAR Study of Resveratrol Derivatives as Potent Inhibitors of Influenza H 1 N 1 Neuraminidase
Author(s) -
Li Chao,
Fang JianSong,
Lian WenWen,
Pang XiaoCong,
Liu AiLin,
Du GuanHua
Publication year - 2015
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.12425
Subject(s) - neuraminidase , quantitative structure–activity relationship , chemistry , resveratrol , in vitro , influenza a virus , cytopathic effect , infectivity , stereochemistry , ic50 , virus , biochemistry , enzyme , virology , biology
The anti‐influenza virus activities of 50 resveratrol ( RV : 3, 5, 4′‐trihydroxy‐trans‐stilbene) derivatives were evaluated using a neuraminidase ( NA ) activity assay. The results showed that 35 compounds exerted an inhibitory effect on the NA activity of the influenza virus strain A/ PR /8/34 ( H 1 N 1) with 50% inhibitory concentration ( IC 50 ) values ranging from 3.56 to 186.1 μ m . Next, the 35 RV derivatives were used to develop 3 D quantitative structure–activity relationship (3 D QSAR ) models for understanding the chemical–biological interactions governing their activities against NA . The comparative molecular field analysis (Co MFA r 2 = 0.973, q 2 = 0.620, q test 2 = 0.661) and the comparative molecular similarity indices analysis (Co MSIA r 2 = 0.956, q 2 = 0.610, q test 2 = 0.531) were applied. Afterward, molecular docking was performed to study the molecular interactions between the RV derivatives and NA . Finally, a cytopathic effect ( CPE ) reduction assay was used to evaluate the antiviral effects of the RV derivatives in vitro . Time‐of‐addition studies demonstrated that the RV derivatives might have a direct effect on viral particle infectivity. Our results indicate that the RV derivatives are potentially useful antiviral compounds for new drug design and development for influenza treatment.