Novel small molecule agonists of anAedes aegyptineuropeptide Y receptor block mosquito biting behavior [article]

Laura B Duvall, Lavoisier Ramos-Espiritu, Kyrollos E Barsoum, J. Fraser Glickman, Leslie B Vosshall
2018 bioRxiv   pre-print
FemaleAedes aegyptimosquitoes bite humans to obtain a blood-meal to develop their eggs. Remarkably, strong attraction to humans is suppressed for several days after the blood-meal by an unknown mechanism. We investigated a role for neuropeptide Y (NPY)-related signaling in this long-term behavioral suppression, and discovered that drugs targeting human NPY receptors modulate mosquito host-seeking behavior. In a screen of all 49 predictedAe. aegyptipeptide receptors, we identified NPY-like
more » ... or 7 (NPYLR7) as the sole target of these human drugs. To obtain small molecule agonists selective for NPYLR7, we carried out a high-throughput cell-based assay of 265,211 compounds, and isolated 6 highly selective NPYLR7 agonists that inhibit mosquito attraction to humans.NPYLR7CRISPR-Cas9 null mutants are defective in behavioral suppression, and resistant to these drugs. Finally, we show that these drugs are capable of inhibiting biting and blood-feeding on a live host, suggesting a novel approach to control infectious disease transmission by controlling mosquito behavior.
doi:10.1101/393793 fatcat:clgj4c6birai5di7vsdsphqdpa