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-alpha] 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 (EC50 = 104 mu g/mL), even superior to that of ningnanmycin (125 mu g/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<bold> </bold>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 CPS52A (219 mu M), CPE204A (231 mu M), and CPR208A (189 mu M) than those with CPWT (5.80 mu M). 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.