Researchers may have discovered a drug that can reduce the ‘thirst’ of ravenous mosquitoes for several days. Findings of the new study were published on 7 February in the journal Cell (1). The compound acts on hormone pathways to trick female mosquitoes into thinking they are full.
Current methods for preventing the spread of mosquito-borne viruses, such as insecticides, repellents, and vaccines, are ineffective; therefore, innovative methods are still badly needed. The Aedes aegypti mosquito is responsible for the spread of pathogenic viruses including yellow fever, dengue, Zika, and chikungunya. These highly dangerous, and sometimes deadly, mosquito-borne infections are passed along by female mosquitoes, which feed on blood to produce and nourish their growing eggs. However, once mosquitoes have consumed enough blood, they stop biting for 2–3 days until their eggs have been laid.
The researchers postured that perhaps by coaxing the blood-sucking disease carriers to feed less often, they could also reduce the spread of certain deadly diseases. The team, led by Prof Leslie Vosshall, a neurobiologist at the Rockefeller University in New York City, discovered that compounds used by the nervous system to communicate hunger in humans can also affect the hormone pathways of mosquitos. In particular, neuropeptide Y-like receptor 7 (NPYLR7) signals to female mosquitoes letting them know whether or not they’re hungry. So, the next step was to determine which compounds activate the receptor. For this, the researchers used high-throughput screening to test more than 265,000 compounds for the best candidates.
One compound, in particular, was found to effectively inhibit biting when Aedes aegypti mosquitoes fed on a solution containing the NPY-activating drug. After consuming the drug ― originally designed to work on human receptors ― the female mosquitos were less interested in the scent of human blood. In other words, the ‘diet drug’ tricked them into feeling full. To verify the results, the researchers also fed the drug to CRISPR-modified with a mutation in the NPYLR7 gene. In this case, the drug no longer had an effect, thereby demonstrating that this particular gene may be the key to inhibiting the appetite of mosquitoes.
This is an exciting finding and the work presents a promising proof of principle. But there is still a lot of work to do in terms of figuring out the best way to exploit the drug for mosquito control. For instance, what is the best way to get the drug into mosquitoes in the wild? Mosquitoes would have to be lured in to drink the compound without attracting other insects. In addition, human drugs cannot be used in the wild since owing to the potential for unwanted effects on people. Therefore, the team is currently working to identify small molecules that activate the NPYLR7 receptor in mosquitoes but not in humans. So far, they have identified six promising compounds, according to Nature.
The new method, if shown to be effective, could offer a promising new approach to disease control. Moreover, the technique could potentially be expanded to other species of mosquito, such as those carrying malaria, as well as other insects like Lyme-disease spreading ticks.
(1) Duvall et al. Novel small molecule agonists of an Aedes aegypti neuropeptide Y receptor block mosquito biting behavior. Cell (2019) DOI: 10.1016/j.cell.2018.12.004