PT - JOURNAL ARTICLE AU - Sean Michael Boyle AU - Tom Guda AU - Christine Krause Pham AU - Sana Khalid Tharadra AU - Anupama Dahanukar AU - Anandasankar Ray TI - Natural DEET substitutes that are strong olfactory repellents of mosquitoes and flies AID - 10.1101/060178 DP - 2016 Jan 01 TA - bioRxiv PG - 060178 4099 - http://biorxiv.org/content/early/2016/06/22/060178.short 4100 - http://biorxiv.org/content/early/2016/06/22/060178.full AB - 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.