Could we fine-tune an antimalarial drug?
A study suggests how subtle changes to a promising drug could provide a better treatment for malaria.
Each year, malaria kills more than 600,000 people, mostly children younger than 5 years old. Humans who have been bitten by mosquitoes infected with malaria-causing parasites become ill as the parasites rapidly multiply in blood cells. Although there are several drugs that are currently used to treat malaria, the parasites are rapidly developing resistance to them, setting off an urgent hunt for new malaria drugs.
Developing new antimalarial medications from scratch is likely to take decades — too long to combat the current public health threat posed by emerging strains of drug-resistant parasites. To speed up the process, scientists are investigating whether drugs developed for other illnesses may also act as therapies for malaria, either when used alone or in combination with existing malaria drugs.
Certain antibiotics — including one called emetine — have already shown promise as antimalarial drugs. These antibiotics prevent the parasites from multiplying by interfering with the ribosome — the molecular machinery in a cell that builds new proteins. However, humans become ill after taking emetine for long periods because it also blocks the production of human proteins.
Tweaking emetine so that it acts only against the production of parasite proteins would make it a safer malaria treatment. To do this, scientists must first map the precise interactions between the drug and the ribosomes in parasites. Wilson Wong, Xiao-chen Bai, Alan Brown and colleagues have now used a technique called cryo-electron microscopy to examine the ribosome of the most virulent form of malaria parasite. This technique uses very cold temperatures to rapidly freeze molecules, allowing scientists to look at molecular-level details without distorting the structure of the molecule — a problem sometimes encountered in other techniques.
The images of the parasitic ribosome taken by Wong, Bai, Brown and colleagues show that emetine binds to the end of the ribosome where the instructions for how to assemble amino acids into a protein are copied from strands of RNA. In addition, the images revealed features of the parasitic ribosome that are not found in the human form. Drug makers could exploit these features to improve emetine so that it more specifically targets the production of proteins by the parasite and is less toxic to humans.
To find out more
Read the eLife research paper on which this eLife Digest is based: “Cryo-EM structure of the Plasmodium falciparum 80S ribosome bound to the anti-protozoan drug emetine” (June 9, 2014).
eLife is an open-access journal that publishes outstanding research in the life sciences and biomedicine.
