A New Molecule Might Be Able To Stop Malaria

Malaria is a big health problem around the world. It is caused by single-celled parasites from the genus Plasmodium and spread by the bite of an infected Anopheles mosquito. Researchers are looking for new ways to fight the parasites that are spread by mosquitoes and cause the disease, as well as new targets that could be used as new ways to fight the parasites.

Now, scientists at the French National Centre for Scientific Research and their partners have found that a new chemical may stop parasites of the genus Plasmodium, which cause malaria, from getting into blood cells.

The results are written up in a piece called “Mechanism of small molecule inhibition of Plasmodium falciparum myosin.” “Informal design of antimalarial drugs” can be found in Nature Communications.


“More than 500,000 people die every year from malaria, and the parasites that cause it, Plasmodium, are becoming resistant to all known agents, including different antimalarial combinations,” the experts wrote. “The myosin motor of the class XIV PfMyoA is part of a core macromolecular complex called the glideosome. The glideosome is needed for Plasmodium parasites to move around, so it is a good drug target. Here, we describe how a small chemical called KNX-002 works with PfMyoA. KNX-002 stops PfMyoA ATPase activity in the lab and stops the growth of asexual blood stage merozoites, which is one of the three stages of Plasmodium’s life cycle that can move.

Malaria bugs are always on the move during their complicated life cycle in humans and mosquitoes. They move through a process called “gliding motility,” which helps them reach, cross, and enter the tissues and cells of their hosts. Gliding is driven by a large group of molecules called the glideosome. At its centre is a class XIV myosin A (PfMyoA) that interacts with short, oriented filaments of divergent actin (PfAct1). This myosin motor is a great therapeutic target for stopping the development of the life cycle.

In several other types of myosin, scientists have been able to make small molecules that can either turn on or turn off the production of force by myosin. KNX-002 was first found to be an inhibitor of PfMyoA in high-throughput actin-activated ATPase screens done by Cytokinetics with 50,000 chemicals from their library. Because PfMyoA is important for invading blood cells, researchers looked at how KNX-002 affected the growth of P. falciparum in its blood stage, the asexual stage.

Their results show that KNX-002 is an inhibitor of PfMyoA activity in vitro. It also slows the growth of asexual parasite blood stages, which is a measure of how well parasites can get into erythrocytes, make copies, leave, and get back in. This is the stage of malaria that causes symptoms.

“We show that KNX-002 blocks PfMyoA by binding to it in a way that hasn’t been described before. This keeps PfMyoA in a post-rigour state where it’s not attached to actin.” “Because KNX-002 stops ATP from being broken down and the lever arm from being primed, motor activity is stopped,” the researchers said.