Purdue researchers have identified a new class of chemical insecticides that could provide a safer, more selective means of controlling mosquitoes that transmit key infectious diseases such as dengue, yellow fever and elephantiasis.
Known as dopamine receptor antagonists, the chemicals beat out the neurotransmitter dopamine to lock into protein receptors that span the mosquito cell membrane.
Disrupting the mechanics of dopamine - which plays important roles in cell signaling, movement, development and complex behaviors - eventually leads to the insect's death.
The researchers used the mosquito genome to pinpoint chemicals that will be more selective than current insecticides, which bind readily to molecules in humans and non-target insects, said Catherine Hill, professor of entomology and Showalter Faculty Scholar.
"These are sophisticated designer drugs," she said. "They're like personalized medicine for mosquitoes - but in this case, the medicine is lethal."
Hill's team showed that DAR antagonists have high potency for both the larval and adult stages of the Aedes aegypti mosquito - which transmits yellow fever, dengue and chikungunya - and Culex quinquefasciatus, the vector of West Nile virus and the disfiguring disease elephantiasis.
Effective pest control has historically been important in slowing the spread of mosquito-borne diseases. But overuse of antibiotics and insecticides has led to the rise of drug-resistant strains of infectious diseases and the emergence of mosquitoes that can withstand conventional pesticides, a "double whammy," Hill said.
"There's an urgent need for new insecticides," she said. "We are seeing a resurgence of infectious diseases that for the last 50 years we had the luxury of controlling with antibiotics and modern medicine. These diseases are increasingly going to become a problem for people everywhere."
The research team designed DAR antagonists to disrupt molecules that are crucial to mosquito survival. The chemicals are structurally distinct from existing insecticides and target a different biochemical path in the mosquito.
The team is mining a group of about 200 DAR antagonists to find the most promising chemicals for commercial products. The insecticides could be cost-effective compared with current products and would have low environmental impact because of their selectivity, Hill said.
The researchers are also taking steps to minimize the risk that the insecticides could bind with human dopamine receptors, said Val Watts, professor of medicinal chemistry and molecular pharmacology and co-author of the studies.
"Many of the compounds we've identified are selective for mosquito receptors versus human receptors - some at a more than one hundredfold," he said. "Also, some of these compounds are already used as treatments for diseases such as schizophrenia and depression. They are safely handled by physicians and pharmacists every day."
The tougher challenge may be ensuring the insecticides do not affect beneficial insects such as honeybees. While the researchers have identified chemicals that are highly selective for mosquito receptors, they are also exploring the possibility of heightening insecticide specificity by using allosteric modulators, molecules that act like dimmer switches, dialing up or down the cell's response to dopamine.
Similar protein receptors exist in the African malaria mosquito, the sand fly and the tsetse fly, suggesting that DAR antagonists could help control these disease-transmitting insects as well.
"We're going after all the big ones," Hill said.
The paper on the effectiveness of DAR antagonists in C. quinquefasciatus mosquitoes was published in PLoS Neglected Tropical Diseases and is available at http://journals.
A proof-of-concept study on using DAR antagonists to control Ae. aegypti was published in The Journal of Pharmacology and Experimental Therapeutics and is available at http://jpet.
Funding for the research was provided by a U.S. Department of Defense Deployed War Fighter Project award, a Purdue Research Foundation Trask Innovation award, and the Indiana Clinical and Translational Sciences Institute, which is funded in part by the National Institutes of Health National Center for Advancing Translational Science.
Natalie van Hoose | EurekAlert!
Light green plants save nitrogen without sacrificing photosynthetic efficiency
21.11.2017 | Carl R. Woese Institute for Genomic Biology, University of Illinois at Urbana-Champaign
Filling intercropping info gap
16.11.2017 | American Society of Agronomy
The WHO reports an estimated 429,000 malaria deaths each year. The disease mostly affects tropical and subtropical regions and in particular the African continent. The Fraunhofer Institute for Silicate Research ISC teamed up with the Fraunhofer Institute for Molecular Biology and Applied Ecology IME and the Institute of Tropical Medicine at the University of Tübingen for a new test method to detect malaria parasites in blood. The idea of the research project “NanoFRET” is to develop a highly sensitive and reliable rapid diagnostic test so that patient treatment can begin as early as possible.
Malaria is caused by parasites transmitted by mosquito bite. The most dangerous form of malaria is malaria tropica. Left untreated, it is fatal in most cases....
The formation of stars in distant galaxies is still largely unexplored. For the first time, astron-omers at the University of Geneva have now been able to closely observe a star system six billion light-years away. In doing so, they are confirming earlier simulations made by the University of Zurich. One special effect is made possible by the multiple reflections of images that run through the cosmos like a snake.
Today, astronomers have a pretty accurate idea of how stars were formed in the recent cosmic past. But do these laws also apply to older galaxies? For around a...
Just because someone is smart and well-motivated doesn't mean he or she can learn the visual skills needed to excel at tasks like matching fingerprints, interpreting medical X-rays, keeping track of aircraft on radar displays or forensic face matching.
That is the implication of a new study which shows for the first time that there is a broad range of differences in people's visual ability and that these...
Computer Tomography (CT) is a standard procedure in hospitals, but so far, the technology has not been suitable for imaging extremely small objects. In PNAS, a team from the Technical University of Munich (TUM) describes a Nano-CT device that creates three-dimensional x-ray images at resolutions up to 100 nanometers. The first test application: Together with colleagues from the University of Kassel and Helmholtz-Zentrum Geesthacht the researchers analyzed the locomotory system of a velvet worm.
During a CT analysis, the object under investigation is x-rayed and a detector measures the respective amount of radiation absorbed from various angles....
The quantum world is fragile; error correction codes are needed to protect the information stored in a quantum object from the deteriorating effects of noise. Quantum physicists in Innsbruck have developed a protocol to pass quantum information between differently encoded building blocks of a future quantum computer, such as processors and memories. Scientists may use this protocol in the future to build a data bus for quantum computers. The researchers have published their work in the journal Nature Communications.
Future quantum computers will be able to solve problems where conventional computers fail today. We are still far away from any large-scale implementation,...
15.11.2017 | Event News
15.11.2017 | Event News
30.10.2017 | Event News
22.11.2017 | Business and Finance
22.11.2017 | Physics and Astronomy
22.11.2017 | Physics and Astronomy