Ferulic Acid Dimers as Potential Antiviral Agents by Inhibiting TMV Self-Assembly.

A series of ferulic acid dimers were designed, synthesized, and evaluated for anti-TMV activity. Biological assays demonstrated that compounds , , and displayed excellent inactivating against tobacco mosaic virus (TMV) with EC values of 62.8, 94.4, and 85.2 μg mL, respectively, which were superior to that of ningnanmycin (108.1 μg mL). Microscale thermophoresis indicated that compounds , , and showed strong binding capacity to TMV coat protein with binding affinity values of 1.862, 3.439, and 2.926 μM, respectively. Molecular docking and molecular dynamics simulation revealed that compound could firmly bind to the TMV coat protein through hydrogen and hydrophobic bonds. Transmission electron microscopy and self-assembly experiments indicated that compound obviously destroyed the integrity of the TMV particles and blocked the virus from infecting the host. This study revealed that can be used as a promising leading structure for the development of antiviral agents by inhibiting TMV self-assembly.