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 had the best inhibitory activity against PVY (EC = 104 μg/mL), even superior to that of ningnanmycin (125 μg/mL). The fluorescence and qPCR results confirmed that compound could inhibit the proliferation of PVY in . Preliminary experiments on the mechanism of action indicated that compound had good binding affinity with the coat protein (CP), which plays an essential role in aphid-PVY interactions. Molecular docking revealed that compound could bind to the pocket of CP formed by Ser52, Glu204, and Arg208. Compound had substantially lower binding affinity () values with CP (219 μM), CP (231 μM), and CP (189 μM) than those with CP (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 provides a unique strategy for the prevention and treatment of PVY.
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