Breathing new life into malaria drugs

Breathing new life into malaria drugs

 Illuminate newsletter, June 2017
June 2017

Laboratory team involved in mefloquine research
Ms Jenny Thompson, Dr Brad Sleebs, Dr Wilson Wong,
Professor Alan Cowman and Mr Tony Triglia (L-R) have
produced an atomic map of how mefloquine works.

Researchers have for the first time mapped how one of the longest-serving malaria drugs works.

The finding opens the possibility of altering its structure to make it more effective and combat increasing malaria drug resistance.

Dr Wilson Wong and Dr Brad Sleebs led the research at the Institute. The study produced a precise atomic map of the frontline antimalarial drug mefloquine, showing how its structure could be tweaked to make it more effective in killing malaria parasites.

Dr Wong said mefloquine had been in use for more than 40 years, yet researchers did not understand how it killed the parasite, until now.

“We discovered that mefloquine attacks the ribosome – the molecular machinery that manufactures proteins required for malaria parasite survival,” he said.

Atomic map shows imperfect fit

However the atomic map of the ribosome and drug-binding site showed the fit was not perfect, Dr Wong said.

“We were able to mimic this interaction with compounds that were able to block the protein machinery and kill the parasite more effectively.”

Mefloquine has been associated with some serious side effects. While mefloquine’s attack on the ribosome was analysed in this study, the authors pointed out that the drug likely targets other parts of the parasite too, killing it through multiple modes of action.

Redesigning a more efficient drug

Dr Sleebs said using the atomic map to redesign the drug to be more targeted would be the next step.

“If we could create a drug that targets this particular mode of action, it could be more efficient and potentially more safe for treating malaria,” Dr Sleebs said.

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