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Updated: Jun 22, 2025
Physiological Recordings and RNA Sequencing of the Gustatory Appendages of the Yellow-fever Mosquito Aedes aegypti
Published on: December 30, 2014
Next-generation neuropeptide Y receptor small-molecule agonists inhibit mosquito-biting behavior
Emely V Zeledon1,2, Leigh A Baxt3, Tanweer A Khan3,4
1Laboratory of Neurogenetics and Behavior, The Rockefeller University, New York, NY, 10065, USA.
Background:
Female Aedes aegypti mosquitoes can spread disease-causing pathogens when they bite humans to obtain blood nutrients required for egg production. Following a complete blood meal, host-seeking is suppressed until eggs are laid. Neuropeptide Y-like receptor 7 (NPYLR7) plays a role in endogenous host-seeking suppression and previous work identified small-molecule NPYLR7 agonists that inhibit host-seeking and blood-feeding when fed to mosquitoes at high micromolar doses.
Methods:
Using structure-activity relationship analysis and structure-guided design we synthesized 128 compounds with similarity to known NPYLR7 agonists.
Results:
Although in vitro potency (EC50) was not strictly predictive of in vivo effect, we identified three compounds that reduced blood-feeding from a live host when fed to mosquitoes at a dose of 1 μM-a 100-fold improvement over the original reference compound.
Conclusions:
Exogenous activation of NPYLR7 represents an innovative vector control strategy to block mosquito biting behavior and prevent mosquito-human host interactions that lead to pathogen transmission.
