Discovery of GPCR-targeted insecticides for malaria mosquito control

Numerous species of mosquitoes are vectors of many pathogens that cause devastating infectious diseases, such as malaria, Dengue, yellow fever, and Zika fever. More than 1 million deaths and up to 700 million cases of infections by mosquito-borne vector diseases (nearly 10% of the total world population) are reported each year. The use of chemical insecticides has been a highly efficient method for the disruption of the pathogen transmission cycle by suppressing the vector population, whereas the evolution of insecticide resistance has hampered the efficacy of currently available classes of insecticides. This study propose to establish a new approach for the development of a novel class of mosquitocidal compounds. In the era of new biotechnology, the search for small bioactive compounds using high throughput screening (HTS) is now a robust and accessible technology that can offer substantive dividends for users. The target molecule for the HTS assay we propose is a G protein-coupled receptor (GPCR), named ecdysis-triggering hormone receptor (ETH-R), which is a receptor for a crucial hormone in the unique biology of arthropods for shedding of their external cuticle during molting and for regulation of another crucial endocrine factor juvenile hormone in mosquito. The ETH-R is an ideal target that will allow for the identification of an effective product with significantly improved selectivity toward mammals and even different orders of insects, which will permit the suppression of the mosquito population without significant environmental damage. Target-based discovery of insecticidal compounds will provide a novel example of a biorational approach for the development of pesticide. 

External Reference Name

Enabling Technologies & Assays
Insecticide Resistance
Vector Control

Dec 2017 — Nov 2019

$430,336

United States