New antimalarial drugs based on an action mechanism linked to the Plasmodium parasite's own biology

Xavier Fernàndez-Busquets

Institute for Bioengineering of Catalonia (IBEC), Barcelona, Spain

In 2022 alone, malaria caused more than 608,000 deaths worldwide, 95 % of them in Africa. The disease is caused by a parasite, Plasmodium, which is transmitted through the bites of mosquitoes of the genus Anopheles. One of the main challenges in combating the disease is that this pathogen very quickly develops resistance to the drugs used against it. This has been the case over the past century, during which Plasmodium first became resistant to quinine derivatives and, more recently, also to artemisinin and related products. This makes it a priority to find new molecules with different mechanisms of action that can circumvent the parasite’s resistance.

One of the most striking features of Plasmodium is that many of its proteins form aggregates. Although the function of these aggregates is not fully understood, they have been shown to be crucial for the parasite’s survival. Understanding the role these aggregated proteins play is essential for designing new drugs aimed at inhibiting this process.

In previous work, the team leading the project developed a highly potent antimalarial drug, YAT2150, which binds strongly to protein aggregates in Plasmodium and against which the pathogen does not appear to develop resistance easily. In this project, the aim is to unravel the precise mechanism of action of this molecule by identifying which proteins it interacts with. The knowledge gained will pave the way for the development of a new generation of antimalarial drugs based on this mechanism of action.

• Diego Muñoz-Torrero, Universitat de Barcelona, Spain

• Zbynek Bozdech, Nanyang Technological University, Singapore

Protein Aggregation in the Malaria PArasite: WHAT for?

€907,923.10