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Discovery & Development Drug Discovery

Paralyze the Parasite

“Imagine a stealth weapon that can be used to launch a self-destruct attack on your vehicle – slamming on the brakes and cutting the engine,” says Leann Tilley of The University of Melbourne (1). No, she doesn’t work in the War Studies department; Tilley is a scientist at the university’s Bio21 Institute and coauthor of a recent paper describing a new and innovative means for combating malaria (2), which still kills hundreds of thousands of people every year (3).

The paper describes the application of ML901, a newly identified antimalarial compound that can hijack and shut down the malaria parasite without damaging its mammalian host. Human cells are not susceptible to any attack from ML901 simply by merit of their structure – it’s a reaction they can’t catalyze.

ML901 enters the malaria parasite aboard an amino acid, then attacks a vulnerable spot – the enzyme tRNA synthetase. Damaging this enzyme breaks the parasite’s protein production engine, quickly neutralizing (to use a military euphemism) the entire organism. Following the attack, the damaged enzyme can only produce a “dead-end product” that then blocks the active site for translation, inhibiting downstream protein synthesis.

Tilley’s team found that ML901 is effective against all stages of malaria’s life cycle, which means there is potential for the treatment to also prevent infection and transmission. And stopping the spread of malaria from the jump is an increasingly important mission in the years ahead, as antimalarial resistance against existing drugs rises ever higher.

Bio21’s work was assisted by Medicines for Malaria Medicine and Takeda Pharmaceuticals, which provided the necessary molecules.

Commenting in a press release (1), Tilley said, “We believe this is just the beginning. We now have the possibility of finding drugs, similar to ML901, that target a range of deadly infectious diseases, including multidrug resistant bacterial infections. The work opens up several new drug discovery avenues.”

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  1. S Juleff, “This parasite will self-destruct: researchers discover new weapon against drug-resistant malaria,” The University of Melbourne (2022). Available at: https://bit.ly/para_para.
     
  2. SC Xie, “Reaction hijacking of tyrosine tRNA synthetase as a new whole-of-life-cycle antimalarial strategy,” Science, 376, 6597 (2022). DOI: 10.1126/science.abn0611.
     
  3. World Health Organization, “Malaria,” (2022). Available at: https://bit.ly/WHO-mal.
About the Author
Angus Stewart

Associate Editor of The Medicine Maker

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