The pervasive and escalating contamination of agricultural ecosystems by insecticides presents a formidable challenge to environmental sustainability, food security, and public health. Conventional chemical pesticides, while effective, have engendered widespread ecological disruption, resistance development, and non-target toxicity. This review systematically elucidates emerging molecular and biochemical targets for next-generation pesticide development, including receptor-mediated signaling pathways such as G‑protein coupled receptors (GPCRs) and nicotinic acetylcholine receptors and critical enzymatic cascades governing chitin biosynthesis, lipid metabolism, and detoxification. Recent advances in RNA interference (RNAi) technologies and regulatory small RNAs (sRNAs) have demonstrated remarkable precision in silencing pest-essential genes, offering environmentally benign alternatives to synthetic insecticides. Additionally, microbial degradation strategies and multi-omics approaches have accelerated the discovery of novel metabolic pathways and biosensors for real-time detection and remediation of pesticide residues. By integrating structural biology, nanotechnology-enabled delivery systems, and computational modeling, this review delineates a comprehensive framework for the rational design and deployment of target-specific pesticides. The synthesis of mechanistic insights with sustainable biotechnological innovations underscores the potential to transcend current limitations, mitigate ecological risks, and inform robust policy frameworks to guide the phased reduction of highly toxic compounds.
Khurram et al. (Tue,) studied this question.