Neuropeptide Y-like receptor 7 (NPYLR7)

Aedes aegypti host-seeking behavior refers to the innate sensory-motor drive of female mosquitoes to locate and feed on human hosts, which is the primary mechanism for the transmission of arboviruses such as Dengue, Zika, and Yellow Fever [11, 14]. While this behavior is a physiological phenotype, it is pharmacologically regulated by specific molecular targets, most notably the Neuropeptide Y-like receptor 7 (NPYLR7) and the Odorant receptor co-receptor (Orco) [1, 7]. NPYLR7 is a G protein-coupled receptor (GPCR) that acts as a master regulator of host-seeking suppression; its activation, normally triggered by endogenous peptides after a blood meal, signals a state of satiety that makes the mosquito non-responsive to human cues like carbon dioxide and skin volatiles for several days [1, 8]. Recent research has identified highly selective small-molecule agonists, such as OA-II and its optimized derivatives like TDI-012631, that exogenously activate NPYLR7 to inhibit biting behavior even in hungry mosquitoes [3, 5]. This approach, known as 'behavioral control,' seeks to disrupt the host-vector interface to reduce disease transmission without relying on broad-spectrum insecticides [1, 2]. Other components of this behavior are targeted by traditional repellents like DEET, which interfere with the Orco-mediated olfactory sensing of host odors [6, 7].

Other names

Mosquito host-seeking behaviorHost-seeking suppression pathwayNPYLR7NPY-like receptor 7AAEL004463Biting behavior

Agonism of the Neuropeptide Y-like receptor 7 to induce a physiological state of satiety and host-seeking suppression, or disruption of chemosensory receptors (e.g., Orco) to block the detection of host-specific volatile organic compounds and carbon dioxide.