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

Potato virus Y (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, C2 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 C2 contributed to its enhanced protective and inactivating activities. Molecular docking revealed that C2 forms a hydrogen bond with arginine 188 (ARG188) in the PVY coat protein (CP). In vivo experiments confirmed the important role of ARG188 in PVY intercellular movement. By competitively binding to ARG188 and activating the plant immune response, C2 significantly reduced PVY pathogenicity. These findings highlight the potential of vanillin-based α-amino phosphonates as effective anti-PVY agents. Specifically, compound C2 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.