Can I wear this odd small molecule to prevent mosquito bites? It's way to early, but interesting..
a tip of the hat to Bryan
Novel small molecule agonists of an Aedes aegypti neuropeptide Y receptor block mosquito biting behavior
Laura B. Duvall1, Lavoisier Ramos-Espiritu2, Kyrollos E. Barsoum1, J. Fraser Glickman2, and Leslie B. Vosshall1,3,4*
1Laboratory of Neurogenetics and Behavior, The Rockefeller University, New York, NY 10065 USA 2High-Throughput Screening and Spectroscopy Resource Center, The Rockefeller University, New York, NY 10065 USA
3Howard Hughes Medical Institute, New York, NY 10065 USA
4Kavli Neural Systems Institute, New York, NY 10065 USA
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.