Compound causes self-destruction of drug-resistant malaria parasites
While improvements continue to be made in anti-malarial drugs and vaccines, the ability of the parasites that cause the disease to mutate and develop resistance to treatment is a chief concern for public health officials. Scientists have discovered a highly-promising new weapon that could help counter this problem, demonstrating how a novel compound that stealthily infiltrates malaria parasites can cause them to self-destruct, importantly, doing so in types with resistance to currently available drugs.
The study was led by scientists at the University of Melbourne, who point to the need for new treatments to help curb the hundreds of thousands of malaria-related deaths each year. Malaria parasites have developed resistance to seven different drugs in the past half century, the scientists note, and although historic vaccines have recently been rolled on vast scales, there is a need for new approaches.
Enter a class of chemicals called nucleoside sulfamates, which the scientists screened to find one in particular that inhibited the growth of the malaria parasite called Plasmodium falciparum, while leaving healthy cells unharmed. Called ML901, the way the molecule does this is as interesting as it is scientifically significant, dismantling the parasite in a way that opens up new avenues for attack from future therapeutics.
"ML901 works by an unusual reaction-hijacking mechanism," said co-lead author Professor Leann Tilley. "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. ML901 finds a particular chink in the machinery that the malaria parasite uses to generate the proteins needed to reproduce itself and stops it doing so."
This effectively makes the parasite self-destruct, according to the scientists, with ML901 binding to an animo acid and destroying the protein production chain the parasite relies on for survival. This was demonstrated in human blood cultures and on animal cells, with ML901 proving effective against malaria parasites with resistance to current drugs, and doing so with rapid and prolonged results. This means it could potentially be used to not just treat the disease but prevent its spread.
"It also shows potential for preventing infected people from transmitting the disease to others, which is critical to stop the spread of malaria," said Tilley.
These promising results provides a springboard for the scientists to pursue next-generation drug treatments for malaria. The next steps include not just searching for drugs with similar effects, but experimenting with tweaks to ML901 to improve its absorption and distribution in the body.
The research was published in the journal Science.