Researchers at TCD are using chemicals borrowed from weedkiller sprays as a way to block malaria, writes Matt Egan
Scientists at Trinity College Dublin are using a type of weedkiller as an unlikely ally in the fight against a disease that kills an estimated 1.5 million people each year.
Dr Gus Bell, who heads the Malaria Research Group at Trinity's department of microbiology, and colleagues, are working with a class of weedkiller that has been found to attack malaria proteins. Bell has been studying malaria at Trinity for 10 years, work funded by the Health Research Board, Enterprise Ireland, and the Higher Education Authority.
Agricultural manufacturers developed the dinitroanaline herbicides for use on food crops, Bell explains. But scientists discovered that they could also block or "inhibit" proteins that are essential for the growth and reproduction of the parasites that cause malaria, he states.
The herbicides attack a protein called "tubulin", which "is generally present in animals and plants but it is also present in malarial parasites", according to Bell. "It is a main constituent in cell skeletons and is essential for cell division."
A drug that attacks malarial tubulin could potentially form the basis of a cure, but it would need to be safe for humans to use.
"Tubulin is also present in humans," Bell explains. To avoid harming humans, a new drug must somehow distinguish between the parasitic and human forms of tubulin. The weedkillers seem to be able to do this.
Unfortunately, "these herbicides are not potent enough to treat the disease effectively so we are looking to develop more potent variants of these chemicals or completely new molecules that fulfil a similar function", says Bell.
The scientists are looking for minute differences in the molecular structure of malarial tubulin, compared to that of human tubulin. These differences could allow drugs to inhibit the parasite molecules but not the human molecules, "so the key is to identify parts of the molecules which are different in the parasite and human versions."
The Malaria Research Group has been doing just that, in collaboration with Dr Neil McFerran of Queen's University Belfast and postgraduate student Brian Fennell,
The scientists now believe they have identified a "groove" on the malarial parasite's protein that is not present in human tubulin although, Bell cautions, "We still have to prove this."
They theorise that an inhibitor drug could be developed containing molecules that could fit into these grooves. Such a drug could prevent the malarial tubulin from functioning properly, without harming the "grooveless" human tubulin. Herbicide molecules are used to help test the theory because they should be able to fit into the malarial tubulin grooves.
Dr Bell is also working with Dr John Walsh, a chemist from Trinity's school of pharmacy, to develop a more potent drug to combat malaria.
Many drugs have been developed to combat the disease in the past but, according to Bell, "drug-resistant" strains of malaria have replaced more treatable varieties. "The most serious resistance is to a drug called chloroquine," because "it was relied on as the major drug for preventing malaria for many years," he states.
Millions of people around the world would benefit from a new cure. "About 40 per cent of the world's population are at risk from malaria because they live in endemic areas," explains Bell. Three hundred million people in the world are likely to have malaria but this, says Bell, is "a conservative estimate. There could be more."