Odour receptors and neurons for detection of DEET and new insect repellents

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.