Antiviral modes of action of the novel compound GLY-15 containing pyrimidine heterocycle and moroxydine skeleton against tobacco mosaic virus

Pest Manag Sci. 2022 Dec;78(12):5259-5270. doi: 10.1002/ps.7147. Epub 2022 Sep 13.

Abstract

Background: Plant virus diseases are difficult to prevent and control, causing serious economic losses to the agricultural production world. To develop new pesticides with antiviral activity, a serial of compounds containing the structure of pyrimidine and moroxydine were synthesized, among which GLY-15 exhibited good antiviral activity against tobacco mosaic virus (TMV), while the mechanism of antiviral activity remains to be clarified.

Results: GLY-15 treatment significantly inhibited the formation of necrotic spots caused by TMV in Nicotiana glutinosa, and effectively suppressed the systemic transportation of TMV expressing a reporter gene (p35S-30B:GFP) in N. benthamiana and markedly reduced the accumulation of a movement deficient TMV in plants as well as viral RNA accumulation in tobacco protoplasts. The results of RNA sequencing showed that GLY-15 induced significant differential expression of genes or pathways involved in the stress response, defense response and signal transduction, phytohormone response and metabolism. Among them, real-time quantitative PCR validated that the expression of 12 critical genes such as heat shock protein, receptor kinase, cell-wall-related protein, disease-related protein and glucan endo-1,3-β-glucosidase were significantly up-regulated. In addition, GLY-15 triggered reactive oxygen species (ROS) production and induced the activity of several crucial defense related enzymes in plants. The results of molecular docking showed potential binding ability of GLY-15 with TMV helicase and the coat protein.

Conclusion: This study provide valuable insights into antiviral mechanism of action for GLY-15, which is expected to be applied as a pesticide for the management of plant viruses. © 2022 Society of Chemical Industry.

Keywords: antiviral mechanism; induced resistance; molecular docking; pyrimidine heterocycle and moroxydine skeleton; transcriptome analysis.

MeSH terms

  • Antiviral Agents / pharmacology
  • Molecular Docking Simulation
  • Nicotiana
  • Plant Diseases
  • Pyrimidines / pharmacology
  • Skeleton
  • Tobacco Mosaic Virus*

Substances

  • moroxydine
  • Antiviral Agents
  • Pyrimidines