Lou Mingshu, Zhu Yunying, Li Jiao, Wu Huan, Zhao Chunni, Shen Zhongjie, Wang Qian, Song Baoan, Song Runjiang
State Key Laboratory of Green Pesticide, Center for R&D of Fine Chemicals of Guizhou University, Guiyang 550025, P. R. China.
J Agric Food Chem. 2025 Jun 18;73(24):14950-14960. doi: 10.1021/acs.jafc.5c03116. Epub 2025 Jun 7.
Phytoviruses depend on intercellular movement to implement systemic infection, which is controlled by several biological macromolecules from pathogens and hosts. Strategically interrupting this process holds promise for plant protection, while few traffic inhibitors are being discovered. In this study, natural coniferylaldehyde is implemented to lead optimization involving dithioacetal modification for virucide discovery. Derivative is screened to show excellent inactivating properties against Potato virus Y (PVY) with a half-maximal effective concentration (EC) of 128.10 μg/mL lower than those of ribavirin (223.08 μg/mL) and vanisulfane (286.13 μg/mL). Combining molecular docking, molecular dynamics simulation, and biolayer interferometry techniques allows verification of residue threonine 155 (T) on PVY coat protein (CP) as the potential targeting site for binding. , treatment and T155A-mutation significantly decrease viral pathogenicity in . Confocal observation reveals the potential function of T is engaged in viral movement between host cells. The study contributes a brand-new lead structure and targeting site for discovering traffic inhibitors.
植物病毒依赖细胞间移动来实现系统感染，这一过程由病原体和宿主的几种生物大分子控制。从战略上阻断这一过程有望实现植物保护，然而目前发现的运输抑制剂很少。在本研究中，采用天然松柏醛进行先导优化，涉及二硫缩醛修饰以发现杀病毒剂。筛选出的衍生物对马铃薯Y病毒（PVY）表现出优异的灭活特性，其半数有效浓度（EC）为128.10μg/mL，低于利巴韦林（223.08μg/mL）和香草硫缩醛（286.13μg/mL）。结合分子对接、分子动力学模拟和生物膜干涉技术，证实了PVY外壳蛋白（CP）上的苏氨酸155（T）残基是该衍生物结合的潜在靶点。该衍生物处理和T155A突变显著降低了植物中的病毒致病性。共聚焦观察揭示了T在宿主细胞间病毒移动中的潜在作用。该研究为发现运输抑制剂提供了全新的先导结构和靶点。
