Find in Library

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 <b>A₁₉</b>, <b>A₂₀</b>, <b>A₂₉</b>, and <b>A₃₁</b> displayed excellent in vivo antiviral curative abilities, affording corresponding EC₅₀ 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 <i>R</i>-forms of target compounds were more beneficial to aggrandize antiviral profiles. Mechanism studies indicate that <b><i>R</i>-A₁₉</b> had a strong affinity (<i>K</i>_d = 5.4 μM) to the TMV helicase and inhibited its ability to hydrolyze ATP (50.61% at 200 μM). Meanwhile, <b>A₁₉</b> could down-regulate the expression of the TMV helicase <i>gene</i> in the host to attenuate viral replication. These results illustrate the excellent inhibitory activity of <b>A₁₉</b> towards the TMV helicase. Additionally, docking simulations uncovered that <b><i>R</i>-A₁₉</b> 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.