Cyclic CAPA peptide analogs targeting the CAPA receptor induce male-specific mortality in western flower thrips.

BACKGROUND: Western flower thrips, Frankliniella occidentalis, is a major agricultural pest that is difficult to manage because of its broad host range, cryptic behavior, rapid population growth, and increasing resistance to conventional insecticides. Insect neuropeptides and their cognate G protein-coupled receptors (GPCRs) have emerged as potential molecular targets for developing alternative pest management tools. In this study, CAPA (capability) neuropeptide analogs were evaluated for their ability to modulate signaling through the F. occidentalis CAPA receptor (CAPA-R) and to reduce thrips survival. RESULTS: Nineteen peptides, including one native ligand, six short linear analogs, six internally cyclized analogs, and six terminally cyclized analogs, were assessed using calcium mobilization assays in Sf9 cells expressing CAPA-R, dual-addition assays, oral feeding bioassays, and in silico receptor-ligand modeling. Most linear peptides and several internally cyclized peptides activated CAPA-R, whereas terminally cyclized peptides showed limited receptor activation in vitro. Peptide feeding assays showed that nine cyclized peptides, including six internally cyclized and three terminally cyclized analogs, significantly reduced the survival of adult male thrips. No significant effects on female survival were detected. Internally cyclized peptides generally showed greater activity in feeding assays than terminally cyclized peptides. Structural modeling further suggested that cyclized peptides interact with the CAPA-R ligand-binding region. CONCLUSION: These findings indicate that cyclized CAPA peptide analogs can reduce the survival of male F. occidentalis and may provide a basis for developing peptide-based control strategies. More broadly, the results support insect neuropeptide GPCRs as promising targets for next-generation pest management approaches. © 2026 Society of Chemical Industry.