title: In vitro antiviral effects and 3D QSAR study of resveratrol derivatives as potent inhibitors of influenza H1N1 neuraminidase.
abstract: 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 (H1N1) with 50% inhibitory concentration (IC50) values ranging from 3.56 to 186.1 μm. Next, the 35 RV derivatives were used to develop 3D quantitative structure-activity relationship (3D QSAR) models for understanding the chemical-biological interactions governing their activities against NA. The comparative molecular field analysis (CoMFA r2=0.973, q2=0.620, qtest2=0.661) and the comparative molecular similarity indices analysis (CoMSIA r2=0.956, q2=0.610, qtest2=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.
authors.affiliation: Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, 100050, China.
authors.forename: Chao
authors.initials: C
authors.lastname: Li
authors.forename: Jian-Song
authors.initials: JS
authors.lastname: Fang
authors.forename: Wen-Wen
authors.initials: WW
authors.lastname: Lian
authors.forename: Xiao-Cong
authors.initials: XC
authors.lastname: Pang
authors.forename: Ai-Lin
authors.initials: AL
authors.lastname: Liu
authors.forename: Guan-Hua
authors.initials: GH
authors.lastname: Du
mesh_terms: D000818:Animals; D000998:Antiviral Agents / Q000737:chemistry* / Q000494:pharmacology*; D002460:Cell Line; D004285:Dogs; D015195:Drug Design; D006801:Humans; D053118:Influenza A Virus, H1N1 Subtype / Q000187:drug effects* / Q000201:enzymology*; D007251:Influenza, Human / Q000188:drug therapy / Q000821:virology; D062105:Molecular Docking Simulation; D009439:Neuraminidase / Q000037:antagonists & inhibitors*; D009976:Orthomyxoviridae Infections / Q000188:drug therapy / Q000821:virology; D021281:Quantitative Structure-Activity Relationship; D000077185:Resveratrol; D013267:Stilbenes / Q000737:chemistry* / Q000494:pharmacology*
chemical_list: D000998:Antiviral Agents; D013267:Stilbenes; D009439:Neuraminidase; D000077185:Resveratrol
keywords: CPE; CoMFA; CoMSIA; NA; RV (3, 5, 4′-trihydroxy-trans-stilbene) derivatives; docking