Navigation Links
NIH funds development of resistance-breaking insecticides to reduce malaria transmission
Date:4/12/2009

Blacksburg, Va. Researchers from Virginia Tech and Molsoft LLC have received a five-year, $3.557 million grant from the National Institute of Allergy and Infectious Diseases (NIAID) to continue their promising work on a new class of resistance-breaking insecticides to reduce malaria transmission.

At present, the first line of defense against the malaria mosquito in sub-Saharan African is insecticide treated nets (ITNs). However, growing resistance to the pyrethroid insecticides used on the nets threatens to render this protection ineffective. The research team led by Paul Carlier (www.files.chem.vt.edu/chem-dept/carlier/), professor of chemistry in the College of Science at Virginia Tech, is striving to develop a new class of insecticides that will be safe for use on nets and effective against pyrethroid-resistant mosquitoes.

The NIAID award builds on results from three years (2005-2008) of research funded by the Foundation for the National Institutes of Health (FNIH) through the Grand Challenges in Global Health initiative of the Bill and Melinda Gates Foundation. This earlier project was led by Jeffrey R. Bloomquist, professor of toxicology and pharmacology in the entomology department of Virginia Tech's College of Agriculture and Life Sciences.

"In 2005, we had a great multidisciplinary team and a promising new idea," said Carlier.

The team combined chemists, entomologists, and biologists in the United States with malaria mosquito control experts in Kenya. The focus was to develop insecticides that strongly interfere with acetylcholinesterase (AChE), a key enzyme in the mosquito brain, while leaving the related human enzyme untouched. The promising new idea was that the malaria mosquito, Anopheles gambiae, would pick up two inactive molecules from a bed net that would then bind to AChE within the mosquito and thus disable it. "That initial concept has not yet been realized," said Carlier.

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 Anopheles gambiae acetylcholinesterases. Totrov, an expert in rational computer-aided drug design methods and in the biophysics of protein-ligand interactions, has worked with Carlier and Bloomquist on the FNIH award since 2006.


'/>"/>

Contact: Susan Trulove
STrulove@vt.edu
540-231-5646
Virginia Tech
Source:Eurekalert

Related biology news :

1. NIH funds research center for womens reproductive health at Einstein
2. Autism Speaks funds $5 million to studies on genetic and environmental risk factors for autism
3. F-MARC funds more soccer and health research
4. More freedom to take risks: DFG funds the first Reinhart Koselleck Projects
5. NIH funds 16 Science Education Partnership Awards
6. NSF funds research at Illinois on sustainable biofuels infrastructure
7. NIAID funds studies of how SARS and bird flu evade antiviral responses
8. Human Microbiome Project awards funds for technology development, data analysis and ethical research
9. NSF funds new Center for the Physics of Living Cells at Illinois
10. NSF funds multi-university center to study environmental implications of nanotechnology
11. NIH EUREKA award funds research at WPI aimed at turning adult skin cells into stem-like cells
Post Your Comments:
*Name:
*Comment:
*Email:
(Date:3/23/2017)... , Mar. 23, 2017 Research and ... System Market Analysis & Trends - Industry Forecast to 2025" ... ... grow at a CAGR of around 8.8% over the next decade ... industry report analyzes the market estimates and forecasts for all the ...
(Date:3/20/2017)... , March 20, 2017 PMD Healthcare ... personal spirometer and Wellness Management System (WMS), a remote, ... Founded in 2010, PMD Healthcare is a Medical Device, ... a mission dedicated to creating innovative solutions that empower ... With that intent focus, PMD developed the first ever ...
(Date:3/7/2017)... England , March 7, 2017 Brandwatch , ... chosen by The Prince,s Trust to uncover insights to ... across The Trust. The UK,s leading youth charity will ... social campaign results and get a better understanding of the topics ... ...
Breaking Biology News(10 mins):
(Date:4/24/2017)... ... April 24, 2017 , ... It ... a cellular milieu; however, the broad application of this cellular target engagement concept ... sensitive quantitative readouts. Cell-based thermal stabilization assays are valuable methods for particular applications, ...
(Date:4/21/2017)... ... April 21, 2017 , ... The University ... first round funding to three startups through the UConn Innovation Fund. The $1.5 ... business startups affiliated with UConn. , The UConn Innovation Fund provides investments of ...
(Date:4/21/2017)... ... April 21, 2017 , ... Frederick Innovative Technology Center, Inc. ... technology-based businesses, recently earned a $77,518 grant from the Rural Maryland Council (RMC) ... FITCI is Frederick’s first incubator. A non-profit corporation, FITCI is a public-private partnership ...
(Date:4/20/2017)... ... April 20, 2017 , ... USDM Life Sciences , the leading risk ... industries, is pleased to announce Holger Braemer as Vice President of its ... based in Germany. , Braemer is an integral part of USDM’s expansion of ...
Breaking Biology Technology: