Researchers trick mosquitoes into thinking they have already fed.

For female mosquitoes, blood provides the nutrients they require to produce eggs. Once they have fed, mosquitoes have no interest in feeding again until they have laid their eggs, which occurs after several days. Earlier studies of mosquitoes have provided evidence to suggest that the desire to feed in mosquitoes is controlled by neuropeptides.

Researchers at Rockefeller University, led by neurobiologist Leslie Vosshall, proposed to target neuropeptide Y (NPY) receptors, which are known to participate in the molecular pathway involved in food-seeking behavior for humans and other animals. Because many human appetite-suppressant drugs target the NPY receptors, the scientists decided to see if these drugs might have an impact on mosquito feeding behavior as well.

The first step was to feed Aedes aegypti mosquitoes solutions containing different NPY-activating drugs (some in development) and see how they reacted to a human-scented lure. The results were promising for one drug in particular: the treated mosquitoes were much less likely to approach the lure than those in a control group, and the effect lasted for two days.

To determine which NPY receptor was involved, the group then grew 49 different mosquito proteins in tissue culture and observed their responses upon exposure to this drug — NPY-like receptor 7 (NPYLR7) appeared to be a strong candidate. Next, using CRISPR gene-editing technology, mosquitoes were created with a mutation in the NPYLR7 gene, which prevented it from functioning properly. As expected, the drug did not affect these mosquitoes.

The next hurdle was finding a non-human drug compound that could potentially be used on mosquitoes in the wild. The researchers screened hundreds of thousands of small molecules and eventually identified six that appear to activate the NPYLR7 receptor and suppress mosquito appetite.

Of course, there are still challenges to overcome. The most potent of the six compounds requires high concentrations to affect mosquito behavior, which would be too costly. Vosshall hopes to partner with medicinal chemists to identify derivatives that will be more effective. There is also the issue of getting the mosquitoes to feed on solutions containing such compounds, which will require traps that mimic humans. The researchers also need to determine if the compounds are effective on other mosquito species.