The mechanism of action of artemisinin and its derivatives, the most potent of the anti-malarial drugs, is not completely understood.

Investigators present an unbiased chemical proteomics analysis to directly explore this mechanism in Plasmodium falciparum.

They use an alkyne-tagged artemisinin analogue coupled with biotin to identify 124 artemisinin covalent binding protein targets, many of which are involved in the essential biological processes of the parasite. Such a broad targeting spectrum disrupts the biochemical landscape of the parasite and causes its death.

Furthermore, using alkyne-tagged artemisinin coupled with a fluorescent dye to monitor protein binding, authors show that haem, rather than free ferrous iron, is predominantly responsible for artemisinin activation.

The haem derives primarily from the parasite’s haem biosynthesis pathway at the early ring stage and from haemoglobin digestion at the latter stages.

These results support a unifying model to explain the action and specificity of artemisinin in parasite killing.

http://www.nature.com/ncomms/2015/151222/ncomms10111/full/ncomms10111.html