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 <b>Q6</b> exhibited potent juvenile-hormone (JH) inhibitory activity against <i>Diploptera punctata</i> and unexpected insecticidal activity against <i><i>Plutella xylostella</i></i>, 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 <i>Ostrinia furnacalis</i>, <i><i>P. xylostella</i></i>, <i><i>Myzus persicae,</i></i> and <i>Acyrthosiphon pisum</i> revealed conserved ligand-binding pockets. The peptide mimic <b>A15</b> exhibited enhanced efficacy against <i>O. furnacalis</i> and <i>A. pisum</i> compared to fenoxycarb and pymetrozine while maintaining activity against <i>P. xylostella</i> and <i>M. persicae</i>. 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 <b>A15</b> as an eco-friendly broad-spectrum IGR candidate.