Binary mixtures of Vanderbilt University allosteric agonist thermolysis components act as volatile spatial repellents for malaria vector mosquitoes

Abstract

BACKGROUND: The development of economically viable and environmentally neutral tools to control insects that consume or damage over 20% of global agriculture or vector human and animal disease represents one of the most important challenges of the 21st century. The suite of chemical-based strategies currently employed to control insect populations rely primarily on insecticides, which are subject to rapid resistance and often have harmful off-target environmental and health-related impacts, and, to a lesser degree, repellents, which typically rely on masking attractive odors. The discovery and characterization of Vanderbilt University allosteric agonists (VUAAs), a family of small-molecule agonists that target the highly conserved, insect-specific odorant receptor coreceptor (Orco), raise the potential for the development of a novel repellent paradigm for vector/pest management. VUAAs have the potential to target nearly all insect olfactory sensory neurons, leading to highly aversive behavioral responses, but importantly have limited volatility, thereby reducing their utility as spatial repellents. RESULTS: We have characterized VUAA thermolysis components and identified a suite of volatiles (VUAA-based active ingredients, VUAIs) that act specifically in novel binary combinations as robust and long-lasting spatial repellents against Anopheline mosquitoes. In mobility-based behavioral experiments, VUAIs act synergistically as effective spatial repellents and outperform parent VUAA compounds against host-seeking Anopheline mosquitoes. CONCLUSIONS: VUAIs are volatile alternatives to Vanderbilt University allosteric agonists (VUAAs) that have the potential for use as spatial repellents in disease vector and agricultural pest control. The repellency observed is odorant receptor coreceptor (Orco)-dependent, supporting the hypothesis that VUAIs and VUAAs similarly target an allosteric Orco recognition site. © 2024 The Author(s). Pest Management Science published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry.