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N,N-Diethyl-m-toluamide, better known as DEET, has been the go-to insect repellent for more than 60 years. But DEET dissolves some plastics and inhibits the mammalian enzyme acetylcholinesterase, which is involved in neurotransmission. Scientists have faced hurdles to finding alternatives to DEET, including a lack of knowledge of which insect receptors are responsible for its repellency and the high cost of identifying and testing substitutes. As part of the search for DEET replacements, Anandasankar Ray and coworkers at the University of California, Riverside, have identified odor receptors and neurons that detect DEET and have developed a computational screening method for identifying new repellents (Nature 2013, DOI: 10.1038/nature12594). The researchers found that a receptor called Ir40a, which is expressed by neurons in fruit fly antennae, responds to DEET and is necessary for DEET avoidance behavior. For the computational screen, the team used shared features of DEET and other known repellents to sift through a library of more than 400,000 compounds. The researchers got approximately 1,000 hits, with about 150 from naturally occurring compounds. They then tested 10 of the compounds on fruit flies and found that eight were repellent. The team also tested four of the compounds in mosquitoes using an arm-in-cage assay that determines whether solutions at 10% concentration repel mosquitoes from treated human arms. All four compounds were effective.
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