Rothamsted Research

Disrupting a mosquito's sense of smell can ward off a bug bite.

Researchers say that they’ve found a new class of chemicals that can drive away mosquitoes by disrupting their odor-sensing system — and the first chemical in that class seems to be thousands of times more effective than DEET.

The compound, called VUAA1, was identified thanks to the kind of high-throughput screening process that is more typically used for drug discovery, said Vanderbilt University professor Laurence Zwiebel, a member of the research team. Zwiebel and his colleagues published their findings online this week in the Proceedings of the National Academy of Sciences.

"This compound is really a first-in-class molecule to do this action," Zwiebel told me today.

A mosquito's olfactory system relies on a variety of receptors spread out on the bug's antennae — known odorant receptors, or ORs. The receptors are tuned to respond to different types of odors, including the smell of sweat and blood, and they activate switches called OR co-receptors (Orcos) to tell the mosquito's brain which scent is being picked up.

Researchers screened almost 120,000 small-molecule compounds to check their effects on human embryonic kidney cells that were genetically engineered to include the OR-Orco complexes.  "It was totally a shotgun approach," Zwiebel said. "Throw the kitchen sink at it and see what happens."

The scientists were surprised to find that VUAA1 consistently activated the odor-sensing complexes, even though it's not actually considered an odorant. "It wasn't something we set out to find. It was an anomaly in our tests," another member of the Vanderbilt team, graduate student David Rinker, said in a news release.

"If a compound like VUAA1 can activate every mosquito odorant receptor at once, then it could overwhelm the insect's sense of smell, creating a repellent effect akin to stepping onto an elevator with someone wearing too much perfume, except this would be far worse for the mosquito," said Patrick Jones, a postdoctoral fellow at Vanderbilt who is the study's first author. 

Zwiebel said that he and his colleagues compared the effectiveness of VUAA1 with that of the widely used DEET insect repellant by measuring how much of each compound it took to repel larval mosquitoes in a petri dish. "The more you use, the more the mosquito moves, as if it's trying to get out of Dodge," he explained. A tiny amount of VUAA1 had the same repellent effect as a concentration of DEET that was tens of thousands of times stronger, Zwiebel said.

However, Zwiebel stressed that VUAA1 isn't yet ready for prime time. "The commercialization of this compound has hardly begun," he said. The chemical still has to be fine-tuned and checked for toxicity, and it's possible that other chemicals in the same class will turn out to be more effective or safer. Vanderbilt University says it has filed for a patent on this class of chemicals and is talking with potential corporate licensees about commercialization, with special focus on the development of products to reduce the spread of malaria in the developing world.

Zwiebel noted that VUAA1 has been found to activate the odor-sensing complexes of flies, moths and ants as well. "Basically, every insect that has an olfactory system has this Orco ion channel," he told me. "We have an expectation that every insect will be affected by this molecule. Now, that's both good and bad."

It's good, because the new class of chemicals may yield new ways to drive away other types of nuisance insects and agricultural pests. But it'd be bad if they also drove away beneficial bugs such as bees and butterflies.

"We've all read 'Silent Spring,'" Zwiebel said. "We don't want to have the same DDT story."

More about mosquitoes:

• Scientists tweak mosquito genes to fight malaria
• A malaria mosquito is quickly becoming two species
• Scientists find natural mosquito repellent
• Researchers studying better insect repellents
• U.N.: Efforts on track to halt malaria deaths

In addition to Jones, Rinker and Zwiebel, authors of "Functional Agonism of Insect Odorant Receptor Ion Channels" include Gregory M. Pask. VUAA1 stands for Vanderbilt University Allosteric Agonist 1. The research was supported by the Grand Challenges in Global Health Initiative, funded by the Foundation for the NIH through a grant from the Bill & Melinda Gates Foundation.

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