Using advanced methodologies that pit drug compounds against specific types of malaria parasite cells, an international team of scientists have identified a new weapon and approach for attacking the parasites that cause malaria.

Principal investigator Elizabeth A Winzeler, from the University of California, San Diego and colleagues found a key metabolic enzyme (phosphatidylinositol 4-kinase or PI4K) that is used for intracellular development by Plasmodium species at each stage of infection in the vertebrate host.

"Most drugs selectively work on certain stages of the (parasite) life-cycle, but not all stages," said Case McNamara, the study's first author and a researcher at the Genomics Institute of the Novartis Research Foundation in San Diego.

"Therefore, inhibitors of this drug target have the potential to not only cure individuals of a malaria infection, but to also prevent infections and even block transmission of the parasite back to the mosquito," said McNamara.

Despite advances in prevention and treatment in recent years, malaria remains one of the world's great infectious scourges.

In 2010, according to the World Health Organisation, there were an estimated 219 million cases globally and 660,000 deaths, mostly among African children, researchers said.

The new approach is far more finely tuned, based on a series of detailed cellular assays that seek to model different parasite life-cycle stages in miniature test tubes.

The researchers looked for the rare compound class that had activities in all parasite stages, but no activity against human cells and which was also drug-like.

A new chemical class, called imidazopyrazines, possessed these properties. The researchers then identified the protein target of these compounds as PI4K.

The disease is caused by Plasmodium parasites, which are transmitted to humans by the infectious bite of an Anopheles mosquito.

Plasmodium vivax and Plasmodium falciparum are the most problematic of the parasite species. The former is the most widespread globally; the latter most deadly.

The discovery could have significant ramifications for eventually eradicating malaria as a global disease. The study was published in the journal Nature.


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