Odour receptors and neurons for DEET and new insect repellents

Abstract

Summary There are major impediments to finding improved DEET alternatives because the receptors causing olfactory repellency are unknown, and new chemistries require exorbitant costs to determine safety for human use. Here we identify DEET-sensitive neurons in a pit-like structure in the Drosophila antenna called the sacculus. They express a highly conserved receptor Ir40a and flies in which these neurons are silenced or Ir40a is knocked down lose avoidance to DEET. We use cheminformatics to screen >400,000 compounds and identify >100 natural compounds as candidate repellents. We test several and find that most activate Ir40a+ neurons and are repellents for Drosophila. These compounds are strong repellents in mosquitoes as well. The candidates contain chemicals that do not dissolve plastic, are affordable, smell mildly like grapes, with three being considered safe for human consumption. Our findings pave the way to discover new generations of repellents that will help fight deadly insect-borne diseases worldwide.

Inhibition of Anopheles gambiae Odorant Receptor Function by Mosquito Repellents

“…These include: activation of specific ORs (the excito-repellent hypothesis (56 -58)); inhibition of specific ORs responding to attractants (59,60); and/or modulation of many ORs causing an olfactory confusion similar in effect but not in molecular terms to the one postulated above for the repellents tested in this study (10,61). In addition, the involvement of ionotropic (62) and gustatory receptors (63) in Drosophila was also demonstrated. Therefore it seems that, in contrast to the case of the Orco function-inhibiting repellents presented in this study, the molecular targets for DEET are fundamentally different.…”

Olfactory Disruption

“…44,79 IRs may be required for responses to repellents in insects. 181 In D. melanogaster, DEET and structurally similar compounds elicit IR40a-dependent responses from a small population of antennal ORNs and avoidance behavior. 181 It is unclear whether these chemically similar compounds are interacting with the same binding site of IR40a or if other downstream molecular components may be involved.…”

Advances in the Identification and Characterization of Olfactory Receptors in Insects

“…This cheminformatics pipeline has been further used to successfully predict new ligands for A. gambiae chemosensory receptors tuned to behaviorally active odorants, leading to the exciting identification of new mosquito repellents 143,144 and attractants (to lure mosquitoes to traps). 144 To use such an approach, it is necessary to have information on functional ligands for the targeted receptor.…”