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bioRxiv · 10.1101/393793

Novel small molecule agonists of an Aedes aegypti neuropeptide Y receptor block mosquito biting behavior

Duvall, L. B.·Ramos-Espiritu, L.·Barsoum, K. E.·Glickman, J. F.·Vosshall, L. B.
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Abstract

Female Aedes aegypti mosquitoes 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 predicted Ae. aegypti peptide receptors, we identified NPY-like receptor 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. NPYLR7 CRISPR-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.

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Duvall, L. B., Ramos-Espiritu, L., Barsoum, K. E., Glickman, J. F., Vosshall, L. B.. 2018-08-16. Novel small molecule agonists of an Aedes aegypti neuropeptide Y receptor block mosquito biting behavior. https://doi.org/10.1101/393793

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