Exploring the potential target of ribavirin inhibiting larvae molting in Spodoptera frugiperda
摘要
Most commercial insecticides target the nerve-muscle system and account for 80% of the total insecticide sales. The insect growth regulators (IGRs) regulate the growth and development of the insects and are generally considered safe for mammals. Ribavirin is an antiviral agent that shows IGR activity against Spodoptera frugiperda. To explore the potential target of ribavirin, transcriptome analysis, metabolomic analysis, histopathological examination, ELISA and molecular docking were conducted. Results suggested that ribavirin showed stomach toxicity to S. frugiperda and caused molting failure. Exposure to sublethal concentrations of ribavirin suppressed the population growth and resulted in negative influence on larvae growth, pupae rate and oviposition. Multi-omics revealed the down regulation of chitin synthase and chitinase, cuticle protein genes. Ribavirin treatment decreased the JHⅠ, JHⅡ, JHⅢ titers but showed no influence on the ecdysone titer. Ribavirin treatment also resulted in the accumulation of JHAMT substrate S-adenosyl-L-methionine, indicating inhibition of JHAMT activity. Ribavirin showed a similar chemical structure to the reported JHAMT inhibitors (nitrogen heterocycle and furanose), and could be well shaped to the pocket of SfJHAMT and shared several same residues with S-adenosyl-L-homocysteine, a natural JHAMT inhibitor. These results indicated that nitrogen heterocycle and furanose are essential for JHAMT inhibitors and ribavirin is a potential JHAMT inhibitor. These results could help identify new IGRs target and provide a lead compound for novel IGRs development.