Researchers at Washington University School of Medicine in St. Louis have identified two crucial enzymes in the malaria parasite's arsenal, and the finding may lead to make of new drugs for the deadly mosquito-borne disease.
The findings have been published in the latest issue of the journal Science.
Of the two enzymes, plasmepsins IX and X, one helps the microbe invade red blood cells; and the other aids the parasite's escape from the cells so it can move on to infect other cells.
The researchers found that by inactivating the genes for the two enzymes, the enzymes are indispensable in getting the parasites into and out of red blood cells.
The parasites without plasmepsin X were able to invade red blood cells and multiply inside them, and then found themselves trapped.
The parasites without plasmepsin IX had the opposite problem: They burst out from red blood cells but were unable to penetrate the next round of cells.
Invading and exiting red blood cells are crucial steps in the life cycle of the malaria parasite. So the two enzymes are just what the researchers are looking for. And a drug that blocks this step would stop the parasite in its tracks.
The researchers then screened compounds known to work on enzymes similar to plasmepsins, and found three that prevent the parasite from multiplying, including one that cured malaria in mice.
Further experiments confirmed that the three compounds target plasmepsin X.
Though one of the three compounds has proven effective in mice, developing it as a potential anti-malarial drug for people probably will require some tweaking to its chemical structure to maximize safety and effectiveness.
