Unveiling the Allatostatin Type-A Receptor as a Promising Target for Discovering the Peptide Mimic A15 as an IGR Candidate with a Broader Insecticidal Spectrum

Allatostatin type-A receptor (AstR-A), a key regulator in insect physiology but not vertebrates, emerges as a promising target. In previous works, allatostatin (AST) analogues Q6 exhibited potent juvenile-hormone (JH) inhibitory activity against Diploptera punctata and unexpected insecticidal activity against Plutella xylostella, indicating that AST analogues may have a broader insecticidal spectrum. However, AstR-A's potential as a promising target for broad-spectrum insect growth regulators (IGRs) has not yet been explored. In this study, phylogenetic analysis underscores its broad-spectrum insecticidal potential. Three-dimensional modeling of AstR-A in Ostrinia furnacalis, P. xylostella, Myzus persicae, and Acyrthosiphon pisum revealed conserved ligand-binding pockets. The peptide mimic A15 exhibited enhanced efficacy against O. furnacalis and A. pisum compared to fenoxycarb and pymetrozine while maintaining activity against P. xylostella and M. persicae. Its mechanism involved disrupting JH/20-hydroxyecdysone biosynthesis and cuticle formation, leading to pest death. These findings highlighted AstR-A as a promising target and A15 as an eco-friendly broad-spectrum IGR candidate.