Development and Mechanism Study of Vanillin-Based α-Amino Phosphonates against Potato Virus Y

<i>Potato virus Y</i> (PVY) is among the top ten plant viruses globally, posing a significant threat to crop yield and quality. Current chemical control agents are limited in variety and offer suboptimal efficiency. To address this, we designed and synthesized a series of new vanillin-based α-amino phosphonate derivatives and evaluated their anti-PVY activities and underlying mechanisms. Among the tested compounds, <b>C2</b> demonstrated the highest protective activity (EC₅₀ = 198 μg/mL), outperforming existing agents such as ningnanmycin (NNM, EC₅₀ = 537 μg/mL), dufulin (EC₅₀ = 495 μg/mL), and vanisufane (EC₅₀ = 210 μg/mL). The α-amino phosphonate moiety in <b>C2</b> contributed to its enhanced protective and inactivating activities. Molecular docking revealed that <b>C2</b> forms a hydrogen bond with arginine 188 (ARG188) in the PVY coat protein (CP). <i>In vivo</i> experiments confirmed the important role of ARG188 in PVY intercellular movement. By competitively binding to ARG188 and activating the plant immune response, <b>C2</b> significantly reduced PVY pathogenicity. These findings highlight the potential of vanillin-based α-amino phosphonates as effective anti-PVY agents. Specifically, compound <b>C2</b> binds to PVY CP ARG188 and impairs PVY mobility, stimulates host immunity, and suppresses viral proliferation, offering a promising foundation for the development of next-generation antiviral agrochemicals.