The Discovery of Novel Ferulic Acid Derivatives Incorporating Substituted Isopropanolamine Moieties as Potential Tobacco Mosaic Virus Helicase Inhibitors.

Target-based drug design, a high-efficiency strategy used to guide the development of novel pesticide candidates, has attracted widespread attention. Herein, various natural-derived ferulic acid derivatives incorporating substituted isopropanolamine moieties were designed to target the tobacco mosaic virus (TMV) helicase. Bioassays demonstrating the optimized , , , and displayed excellent in vivo antiviral curative abilities, affording corresponding EC values of 251.1, 336.2, 347.1, and 385.5 μg/mL, which visibly surpassed those of commercial ribavirin (655.0 μg/mL). Moreover, configurational analysis shows that the -forms of target compounds were more beneficial to aggrandize antiviral profiles. Mechanism studies indicate that had a strong affinity ( = 5.4 μM) to the TMV helicase and inhibited its ability to hydrolyze ATP (50.61% at 200 μM). Meanwhile, could down-regulate the expression of the TMV helicase in the host to attenuate viral replication. These results illustrate the excellent inhibitory activity of towards the TMV helicase. Additionally, docking simulations uncovered that formed more hydrogen bonds with the TMV helicase in the binding pocket. Recent studies have unambiguously manifested that these designed derivatives could be considered as promising potential helicase-based inhibitors for plant disease control.