Sunday , August 1 2021

They destroy hunger in a mosquito that transmits dengue

With less than a thousand grams of gram and a maximum speed of less than three kilometers per hour, the female mosquito is one of the most dangerous animals on the planet, because, when flying from person to person, we are caught trying to extract the blood he needs to store eggs. This small creature transmits microbes that kill and kill millions of people every year.

However, scientists at Leslie B. Vosshall's laboratory at Rockefeller University in the United States have shown that you can "persuade" female mosquitoes not to bite. His work, published in the Cell magazine, illuminates the behavior of host searchers and the feeding of blood that poses a threat to these insects, and can lead to new ways to halt these movements and eliminate portable species.

The researchers carried out their experiments with mosquitoes Aedes aegypti, responsible for the spread of dengue, zike, chikungunya and yellow fever. Aedes women are very attractive to people whose blood contains proteins they need to produce their eggs. But when they feed, the attraction is greatly reduced, and mosquitoes show little interest in looking for another "food" for a few days.

"It's like the best Thanksgiving dinner," says a colleague who led the project, Laura Duvall. Scientists can reproduce this long-term satiety effect by injecting female mosquitoes with high doses of molecules called neuropeptides that activate specialized receptors.

However, a list of possible combinations of neuropeptide receptors is long, and it is therefore necessary to develop compounds that can effectively prevent the behavior of women who do not consume other adverse reactions. Similar receptors regulate nutritional behavior in many species, including in humans. And precisely this common evolutionary heritage was the one the researchers needed.

Special receiver

In humans, neuropeptide receptors, called Y or NPY, regulate the intake of food. The pharmaceutical industry has developed anti-obesity drugs that activate or inhibit them. Duvall and his colleagues thought that the same medicines could affect mosquitoes, and so it was. When mosquitoes were fed with a solution with medicines that activated NPY human receptors, the inwardness of the insects towards the human host collapsed as if they had a "purging" of blood. If mosquitoes were fed with a drug that inhibited these same receptors, they behaved like they did not eat. To identify a particular receptor on which human medicines operated, we used knowledge of mammon genome to clone 49 possible neuropeptide receptors and exposed them to the same compounds. Only one, a receptor known as NPYLR7, responded to all medicines that affected mosquitoes.

"We were thrilled to have drugs that affect the human appetite perfectly work to crush the appetite of mosquitoes," says Vosshall. Moreover, when the team fed the Aedes mutated mosquito net, which was designed to have no NPYLR7 receptors, they were still interested in "than ever at the next meal", which confirmed that the recipient was NPYLR7 recipient.

Another step

However, medicines for humans were not suitable for use in nature, as they can affect people and mosquitoes. They began to search for molecules that selectively activate NPYLR7 from mosquitoes without activating human NPY receptors. Beginning with a list of more than 250,000 candidates, the team finally opted for "Compound 18", a molecule that, without further effects, reduced the behavior of Aedes in the search for hosts. The researchers placed a live mouse in front of mosquitoes. Although Aedes prefers people, they are in line with other mammals. The mosquitoes that were fed with "compound 18" were so uninterested in the mouse as mosquitoes who enjoyed a "meal" of blood.

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