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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.
Parasites & Vectors
|June 27, 2024
Summary
Researchers developed new compounds that significantly reduce mosquito blood-feeding behavior. This discovery offers a novel strategy for controlling disease-carrying mosquitoes by targeting Neuropeptide Y-like receptor 7 (NPYLR7).
Area of Science:
- Vector biology
- Chemical biology
- Entomology
Background:
- Female Aedes aegypti mosquitoes transmit pathogens during blood meals.
- Host-seeking behavior is suppressed post-blood meal until egg-laying.
- Neuropeptide Y-like receptor 7 (NPYLR7) regulates endogenous host-seeking suppression.
Purpose of the Study:
- To discover novel small-molecule agonists of NPYLR7.
- To identify compounds that inhibit mosquito host-seeking and blood-feeding behaviors.
Main Methods:
- Synthesized 128 compounds using structure-activity relationship analysis and structure-guided design.
- Evaluated compound efficacy in inhibiting mosquito blood-feeding from a live host.
Main Results:
- Identified three potent NPYLR7 agonists.
- Achieved a 100-fold improvement in efficacy, reducing blood-feeding at 1 μM dose.
- In vitro potency did not strictly predict in vivo effectiveness.
Conclusions:
- Exogenous activation of NPYLR7 is a promising vector control strategy.
- Blocking mosquito biting behavior can prevent pathogen transmission.
- Targeting NPYLR7 offers innovative approaches to combat vector-borne diseases.
