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- 12 December 2013 1:00 pm , Vol. 342 , #6164
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Malaria Drug’s Secret Is Out
20 August 2003 (All day)
Chinese doctors have prescribed it for thousands of years, and even today, it's one of the most effective treatments for malaria. Now, scientists say they have finally discovered exactly how a plant-derived drug called artemisinin kills malaria parasites. The finding may help develop new weapons against malaria.
Artemisinin and several derivatives are derived from qinghao, also known as sweet wormwood or Artemisia annua, a plant long known for its fever-reducing abilities. Qinghao extracts have recently become very popular in Southeast Asia, where resistance to most other malaria drugs is rampant, and more and more researchers are studying the drugs. But exactly how artemisinin kills the Plasmodium falciparum parasite that causes malaria remained unclear. Artemisinin has a chemical structure called a peroxide bridge, which can be cleaved by iron ions to form free radicals that attack a range of proteins and other biomolecules; some researchers suspected that such an attack would be fatal for the parasites. Others speculated that, like the malaria drug chloroquine, artemisinin frustrates the removal of haem, a toxic byproduct formed during the parasite's consumption of human hemoglobin.
Neither of those explanations is right, according to a team from the University of Liverpool, the University of Southampton, and St. George's Hospital Medical School in the U.K. The team noted that the chemical structure of artemisinin resembles thapsigargin, an inhibitor of an enzyme found in the cells of mammals. Perhaps artemisinin does something similar, they reasoned--and sure enough, artemisinin proved a specific and very potent inhibitor of a similar enzyme, called PfATP6, in Plasmodium. A series of experiments confirmed that the drug's ability to block PfATP6 is also what thwarts the parasites.
“I believe their data and I think they have a very strong argument,” says molecular epidemiologist Steven Meshnick of the University of North Carolina, Chapel Hill. Still, he says he's not totally convinced yet; the ideal way to nail PfATP6 as artemisinin's target would be to find a Plasmodium strain that's resistant to artemisinin and show that they have a mutation in the gene for PfATP6, he says. Until now, no such resistant strains have been found in patients--and nobody is hoping to see them anytime soon.