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Background <p>The chemical management of potato virus Y (PVY)-induced viral diseases in <i>Solanaceae</i> 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 <i>Poaceae</i> 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.</p> Result <p>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 EC<sub>50</sub> value (169.4&#xa0;µg/mL) than the commercial control ribavirin (244.7&#xa0;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 <i>Agrobacterium</i>-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.</p> Conclusion <p>The study successfully developed L5, a benzoxazinoid-derived compound originating from secondary metabolites of <i>Poaceae</i> 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.</p>

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

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年10月6日

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  • Yuefei Long,
  • Chunni Zhao,
  • Huan Wu,
  • Zhongjie Shen,
  • Baoan Song,
  • Deyu Hu

摘要

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.