Discovery of Pyrido[1,2-α] Pyrimidinone Mesoionic Compounds as Potential Control Agents Against Potato Virus Y.

Potato virus Y (PVY) relies on aphids and tubers to spread in the field and causes serious economic losses in the potato industry. Here, we found that pyrido[1,2-α] pyrimidinone mesoionic compounds with insecticidal activity against aphids possessed a good inhibitory effect on PVY. Among them, compound 35 had the best inhibitory activity against PVY (EC ₅₀ = 104 μg/mL), even superior to that of ningnanmycin (125 μg/mL). The fluorescence and qPCR results confirmed that compound 35 could inhibit the proliferation of PVY in Nicotiana benthamiana . Preliminary experiments on the mechanism of action indicated that compound 35 had good binding affinity with the coat protein (CP), which plays an essential role in aphid-PVY interactions. Molecular docking revealed that compound 35 could bind to the pocket of CP formed by Ser52, Glu204, and Arg208. Compound 35 had substantially lower binding affinity ( K _d ) values with CP ^S52A (219 μM), CP ^E204A (231 μM), and CP ^R208A (189 μM) than those with CP ^WT (5.80 μM). A luciferase assay confirmed that mutating Ser52, Glu204, and Arg208 significantly affected the expression level of CP and further reduced virus proliferation. Therefore, the broad-spectrum activity of compound 35 provides a unique strategy for the prevention and treatment of PVY.