What is it about?
Malaria parasites, and their relatives, move and invade our cells using a tiny molecular motor called myosin A. This study describes KNX-115, a molecule that jams that motor. In the lab, blocking the motor stopped the malaria parasite at several different points in its life cycle — in the blood, in the liver, and in the mosquito stages that spread the disease — and it worked even against parasites that already resist today's antimalarial drugs, including samples taken directly from patients in the Brazilian Amazon. Because closely related parasites use a very similar motor, the same molecule also blocked Cryptosporidium, Toxoplasma, and Eimeria, which cause serious disease in people, animals, or both. The team also determined the detailed 3-D structure of the molecule locked onto the motor, showing exactly how it works. KNX-115 is a research tool used to prove that this motor is a good drug target — not a medicine itself.
Featured Image
Photo by National Institute of Allergy and Infectious Diseases on Unsplash
Why is it important?
Malaria still causes an estimated 610,000 deaths a year, most of them young children, and the parasite keeps evolving resistance to the drugs we have. Almost all current antimalarials work in a handful of similar ways, so the parasite has repeatedly found escape routes. This work shows that targeting the parasite's motor is a genuinely different approach — one the parasite appears to struggle to evade, since the molecule stays effective against already-resistant strains and the resistance that did emerge came at a cost to the parasite. Establishing myosin A as a solid, druggable target gives drug hunters a new foundation to build on, not just for malaria but potentially for a whole family of related parasites that affect human and animal health.
Perspectives
Myosins — the molecular motors that drive movement inside cells — have long been our focus, and they've already proven to be druggable in human disease: myosin-targeting molecules have reached the clinic for heart conditions, including an FDA-approved treatment for hypertrophic cardiomyopathy. Our philosophy has been that if you understand a target well enough at the molecular level, you can design molecules against it rationally rather than by trial and error. This study extends that thinking to the parasite's own motor, myosin A. Decades of cytoskeletal biology made it possible to determine exactly how this motor works and to find a molecule, KNX-115, that traps it precisely where it is vulnerable. For us, the point was to prove that myosin A is a genuinely druggable target — that inhibiting it can stop the parasite at multiple stages of its life cycle. KNX-115 is the tool that let us establish that. This was a terrific collaboration among many highly accomplished groups around the world, whose complementary expertise made the breadth of this work possible. Together, it lays the groundwork for a new generation of molecules against malaria and other apicomplexan parasites that affect both humans and animals.
Darshan Trivedi
Read the Original
This page is a summary of: Antimalarial cytoskeletal targeting with broad apicomplexan activity, Proceedings of the National Academy of Sciences, July 2026, Proceedings of the National Academy of Sciences,
DOI: 10.1073/pnas.2608709123.
You can read the full text:
Contributors
The following have contributed to this page
