Discovery of 110 new proteins could help design more precise and potent repellents

Every year diseases carried by mosquitoes — notably malaria, dengue and filariasis — claim over a million lives. A discovery by scientists at the National Centre for Biological Sciences (NCBS), Bangalore could however signal the possibility of “new strategies” to prevent the primary point of contact between mosquitoes and humans. By targeting its notoriously keen sense of smell, the mosquito’s ability to home in on humans can be prevented.

According to a paper published in the Genome Biology and Evolution journal, a group of 110 proteins discovered in three disease-transmitting mosquito species — Anopheles gambiae and Aedes aegypti (which spreads dengue, chikungunya and yellow fever), and Culex quinquefasciatus (carrier of lymphatic filariasis) — are central to the mosquito’s olfactory system and could become key targets for more precise and potent repellents.

The olfactory process begins with these ‘odorant binding proteins’ (OBPs) that bind molecules carrying the scent of their prey and help direct the parasite to its host.

All repellents work by interfering with the proteins and compromising the insect’s ability to sniff out its prey. But the discovery of 110 OBPs will increase the number of proteins that can be targeted by repellant molecules. “When the OBP is inhibited, the protein cannot recognise odour molecules, which means the odours will never be transported to the olfactory receptors that direct mosquitoes to the host,” explains Malini Manoharan, a postdoctoral fellow at NCBS who co-authored the paper with Ramanathan Sowdhamini, Professor at NCBS and others.

Primary prevention is one of the most important ways to cut the spread of disease “either by controlling the mosquito population or by preventing the interaction between the mosquitoes and the host,” the authors point out. The World Health Organization had warned of climate change causing an expanse in the range of mosquitoes and “heightening the risk of disease for millions of additional people.”

Interestingly, while this olfactory mechanism is similar in all mosquito species, the authors noticed more OBPs in A. aegypti and C. quinquefasciatus mosquitoes compared with A. gambiae. “Knowing the structures for these domains could lead to the design of better repellents,” says Prof. Sowdhamini.

The additional OBPs belong to three classes — Classic, PlusC and Dimer OBPs — each of which is believed to bind to different odourant molecules. The Dimer OBPs in mosquitoes have been reported for the first time in this study opening new avenues of research.

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