Discovery of Poaceae-based virion-assembly inhibitor for managing potato virus Y.

Abstract

Background: The chemical management of potato virus Y (PVY)-induced viral diseases in Solanaceae crops remains a persistent challenge. Successful systemic infection and transmission of PVY depend on the formation of intact virions, suggesting that targeted inhibition of coat protein (CP)-mediated encapsidation of viral RNA could disrupt viral assembly. However, reported inhibitors capable of disrupting such a process remain scarce. The present study reports a series of analogues derived from benzoxazinoids-allelopathic secondary metabolites of Poaceae plants-and systematically evaluates their anti-PVY activity. Furthermore, the preliminary mode of action of the most potent compound to impair viral assembly is elucidated.

Result: Thirty-four benzoxazinoids (L1-L34) containing sulfonamide moieties were synthesized via a three-step reaction protocol and evaluated for their virucidal activity using the half-leaf local-lesion assay. Most compounds demonstrated promising inactivation potency, with derivative L5 exhibiting a lower EC₅₀ value (169.4 µg/mL) than the commercial control ribavirin (244.7 µg/mL). Molecular docking, dynamics simulations, and bio-layer interferometry revealed that VAL211 (V211) on the PVY CP likely serves as the critical binding residue for L5. Notably, in Agrobacterium-mediated infection assays, the V211A mutant virus exhibited markedly attenuated fluorescence intensity, while confocal microscopy confirmed unimpaired viral cell-to-cell movement. Conversely, transmission electron microscopy revealed a significant reduction in both viral particle quantity and length, suggesting that L5 inhibited CP-mediated viral RNA assembly.

Conclusion: The study successfully developed L5, a benzoxazinoid-derived compound originating from secondary metabolites of Poaceae plants, which exhibited exceptional anti-PVY activity through serving as an inhibitor of virion assembly. These findings position L5 as a promising lead compound for the rational development of novel virion assembly inhibitors targeting CP-dependent processes in PVY and related plant viruses.