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 (EC50 = 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 CPS52A (219 μM), CPE204A (231 μM), and CPR208A (189 μM) than those
with CPWT (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.