Anandasankar Ray | Search bioRxiv

bioRxiv2016

Natural DEET substitutes that are strong olfactory repellents of mosquitoes and flies

Despite shortcomings, N,N-Diethyl-3-methylbenzamide (DEET) has remained the gold-standard of insect repellents for >60 years. There are significant impediments to finding improved substitutes because the molecular targets causing repellency are unclear, new chemistries will require significant human-safety testing, and predicted costs for development are exorbitant. Here we identify shared structural features important for repellency and using a supervised chemical-informatics method screen insilico >400,000 compounds to identify >100 natural compounds as candidate repellents. We select 4 candidates that are affordable, 3 approved as safe for human food use, and demonstrate that they are strong olfactory and gustatory repellents to both mosquitoes and Drosophila. The chemicals do not dissolve plastic and have a mild and pleasant odor. These repellents are representative of a new generation of affordable substitutes for DEET that can be rapidly deployed globally because of excellent human-safety profiles, and have great potential in reducing deadly diseases by reducing mosquito-human contact.

Neuroscience↗

bioRxiv2015

Repellent compound with larger protective zone than DEET identified through activity-screening of Ir40a neurons, does not require Or function

The widely used insect repellent DEET has a limited spatial zone of protection, requiring it to be applied over all exposed areas of skin. Identification of insect DEET-sensing neurons expressing a highly conserved Ionotropic receptor, Ir40a, provides an opportunity to identify new structural classes of volatile agonists as potential spatial repellents. By imaging the activity of the Ir40a+ neurons in D. melanogaster expressing the calcium sensitive GCaMP3 protein, we identify a strong agonist, 4-methylpiperidine, with a much higher vapor pressure than DEET. Behavioral testing reveals that 4-methylpiperidine repels Aedes aegypti, which is consistent with our model that Ir40a marks a conserved innate aversive pathway. Using a spatial repellency assay we demonstrate that 4-methylpiperidine applied to one part of the hand repels mosquitoes on another part effectively, whereas DEET cannot do so. Using orco mutant A. aegypti we demonstrate that avoidance to 4- methypiperidine is not dependent on Or family function. Additional testing of orco mutant mosquitoes demonstrates that they are also effectively repelled by DEET, without coming in contact with it, in heat attraction assays. Together, these results support our initial observations that the conserved Ir pathway plays a key role in olfactory repellency and can be used to identify new classes of repellents.

Neuroscience↗