Over 100 proteins targeted by the antimalarial drug artemisinin are identified in an article published in Nature Communications. The study also shows that artemisinin is activated by a specific iron-containing compound called heme.
Activation of artemisinin - currently the most effective drug against malaria - requires the presence of ferrous iron, but the nature of the iron source and the identity of the proteins targeted by the drug have long been controversial.
Qingsong Lin and colleagues develop chemically-tagged artemisinin analogues to visualize the proteins targeted by the drug in Plasmodium falciparum, the most pathogenic malaria parasite to infect humans. They identify 124 proteins to which the drug, once activated, binds irreversibly. Many of these proteins are involved in essential biological processes in the parasite, which would explain why artemisinin is such an effective drug. In addition, the researchers show that heme is the main source of the iron that activates the compound.
Although additional drug targets are likely to exist, these findings help to understand how artemisinin kills the malaria parasite. The authors also propose that the results may help to facilitate the development of better alternative strategies to treat malaria, given current emergence of artemisinin resistance in certain parts of the world.
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