Another malaria breakthrough offers potential drug target

In the second breakthrough this week by Australian scientists tackling the spectre of malaria, researchers at the Walter and Eliza Hall Institute (WEHI) have identified a key protein that aids the spread of the malaria parasite through the bloodstream.

This protein represents a possible drug target that could potentially halt the spread of the malaria parasite, thus stopping it in its tracks.

The challenge in battling malaria is that the parasite, Plasmodium falciparum, is able to enter in to red blood cells and hide itself from the immune system.

Professor Alan Cowman, head of the WEHI's Infection and Immunity division, said the parasite remodels the red blood cells by exporting hundreds of so- called ‘effector’ proteins into the cytoplasm of the red blood cell.

“These are key virulence proteins that allow the parasite to survive in the human and hide from the human immune system,” Professor Cowman said.

Cowman and his team went on the hunt for the mechanism that enables these effector proteins to be exported, and they believe they have found it in a protein called Plasmepsin V.

Professor Cowman said experimentation had shown that the action of Plasmepsin V on the effector proteins was the first step in priming the proteins to be exported beyond the parasite’s membrane into the red blood cell cytoplasm.

“Plasmepsin V is responsible for determining that all the hundreds of effector proteins are exported. If we could find drugs to block Plasmepsin V the malaria parasite would die,” he said.

Professor Cowman said because Plasmepsin V was a protease it was an attractive drug target. “Drugs that target proteases have been very effective in combating HIV so, by analogy, drugs that impede the function of Plasmepsin V should also show promise,” he said.

The hope is that a drug can be developed that inhibits Plasmepsin V, thereby preventing malaria from being able to enter red blood cells.

Collaborators on the research include Dr Justin Boddey, Dr Tony Hodder, Dr Svenja Gunther, Dr Andrew Pearce and Professor Cowman from the institute, in collaboration with Professor Richard Simpson, Dr Heather Patsiouras and Dr Eugene Kapp of the Ludwig Institute for Cancer Research, Professor Brendan Crabb and Paul Gilson at the Burnet Institute and Dr Tania de Koning-Ward at Deakin University.

The research was funded by the National Institutes of Health, the National Health and Medical Research Council and the Howard Hughes Medical Institute.

The paper was published in Nature today.