However, the team made two important advances which form the basis for the NIAID grant for "Development of vector-specific, resistance breaking insecticides to reduce malaria transmission."
"First, we discovered we could modify the chemical structures of existing AChE-targeting insecticides in a way that should significantly lower their toxicity to mammals," said Carlier. Since these compounds still retain significant insecticidal activity against the malaria mosquito, they could prove ideal for deployment on ITNs. Two patent applications have been filed and commercial interest has been expressed in the potentially safer compounds, he said.
"Second, we figured out how to inhibit target site-resistant mosquito AChE and demonstrated this effect in vitro," said Carlier. "The challenge now is to modify these inhibitors so that they can make their way into the mosquito's brain and thus exert the desired insecticidal action."
The new insecticides should also be less likely to cause the emergence of new target site-resistant strains, he said. And the team has developed a number of other strategies to ward against metabolic resistance mechanisms in the Anopheles gambiae mosquito.
In addition to principal investigator Carlier and co-investigator Bloomquist, other co-investigators on the NIAID-funded research team are Jianyong Li, associate professor of biochemistry in the College of Agriculture and Life Sciences at Virginia Tech, and Maxim Totrov, principal scientist at Molsoft LLC of La Jolla, Calif.
Carlier is responsible for the design of synthetic routes to the AChE-based insecticides. Bloomquist is responsible for the pharmacological and toxicological assessment of the proposed insecticides. Li, who has extensive experience in isolating and crystallizing a number of important mosquito enzymes in native form, is responsible for expressing, purifying, and crystallizing various Anophele
|Contact: Susan Trulove|