Although the widely-used insect repellent DEET has been around for over 60 years, it is only now that scientists have been able to uncover how mosquitoes and the like smell this chemical, causing them to turn away in disgust.

Working on the fruit fly, Anandasankar Ray and his team at the University of California at Riverside in the U.S. were able to identify the molecule on an insect’s smell-sensing nerve cells that acts as a receptor for DEET. (DEET is an abbreviation for N,N-diethyl-meta-toluamide.)

The discovery of this receptor and the neurons that carry it allowed the scientists to screen nearly half a million compounds, looking for improved alternatives to DEET. Several natural compounds, including three with a mild grape-like aroma that had been approved as food additives, showed promising results.

“Novel repellents that are safe and affordable can be used to limit insect-human contact in disease-endemic areas of the world and to provide an important line of defence against deadly vector-borne diseases,” they pointed out in a paper just published in Nature.

Finding insect receptors for a particular odour was “a hard job”, said Gaiti Hasan, senior professor at the National Centre for Biological Sciences in Bangalore, commending the work.

As many other scientists had previously tried to find the receptor, “we realised right away that there had to be something elusive about it,” Dr. Ray told this correspondent. So “we had to cast our net broadly.”

He and his colleagues turned to a recently developed technique involving the much-studied fruit fly, Drosophila melanogaster. Strains of this fly were genetically engineered so that its sensory neurons produced a green fluorescent protein when stimulated by an odour. The neurons that glowed green when exposed to DEET turned out to be in a pit-like structure in the antenna of the fly.

They went on to establish that a protein known as Ir40a was the DEET receptor that activated those neurons.

The researchers then set out to look for better DEET substitutes. DEET’s high cost and the inconvenience of keeping skin slathered with the chemical at high concentrations have limited its use in many countries where mosquito-borne diseases are rife. Besides, it dissolves plastics and synthetic fabrics, and safety concerns have also been raised.

Based on features shared by DEET and other known repellents, the team created a computer programme that could examine structural information about various chemicals and quickly identify those that might be most effective in stimulating the Ir40a-bearing nerve cells. The programme was used to screen close to half a million compounds, including over 3,000 naturally occurring ones.

“Because we were able to screen so many, we obtained a very large list of potential new repellents,” remarked Dr. Ray.

Ten natural compounds identified in the screen were tested in fruit flies. Eight of them activated Ir40a neurons and displayed good repellence. Four of those molecules were also shown to be capable of repelling female Aedes aegypti mosquitoes, which can spread the viruses that cause dengue and chikungunya.

Three of those four natural compounds had already been cleared as food additives, greatly simplifying the process of getting regulatory approval for their use as insect repellents, pointed out Dr. Ray. Another 150 natural compounds were still to be tested.

His lab had begun looking for molecules that could out-perform DEET, he said.

The characteristics being sought included being effective at lower concentrations than DEET and for longer durations and also the ability to repel mosquitoes at a greater distance.

Since the DEET receptor was very similar in many different species of insects, there were also exciting possibilities for identifying cheap, non-toxic repellents to ward off agricultural pests that caused enormous crop losses, added Dr. Ray.

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