In vitro Antiviral Effects and 3D QSAR Study of Resveratrol Derivatives as Potent Inhibitors of Influenza H1N1 Neuraminidase

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, q_test² = 0.661) and the comparative molecular similarity indices analysis (CoMSIA r² = 0.956, q² = 0.610, q_test² = 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.