A recent study published in Nature Microbiology identifies FIKK kinases, a unique family of proteins in Plasmodium falciparum, as promising targets for new malaria treatments.

Researchers from the Francis Crick Institute and Gulbenkian Institute analyzed over 2,000 samples of P. falciparum, discovering that 18 of the 21 FIKK kinase genes are essential for the parasite's ability to infect humans.

Blocking all FIKK kinases simultaneously could hinder the parasite's capacity to modify host cells, potentially leading to a new class of antimalarial drugs with a lower risk of resistance.

In collaboration with GlaxoSmithKline, the research team screened various compounds to inhibit FIKK kinases, identifying three candidates that effectively blocked most kinases in laboratory tests.

FIKK kinases play a critical role in modifying host red blood cells, which can lead to severe complications such as blood clots during malaria infection.

Lead researcher Moritz Treeck emphasized that FIKK kinases are vital for the survival of Plasmodium in both humans and great apes, suggesting a shared evolutionary trait that could be targeted therapeutically.

The study revealed that one FIKK kinase specifically targets the amino acid tyrosine, marking a novel discovery for parasitic proteins and indicating its role in host cell signaling pathways.

Using AlphaFold 2, researchers mapped the structures of FIKK kinases, identifying a flexible loop region that varies among kinases, which may provide insights for targeted drug design.

The FIKK kinase family consists of 21 paralogues in P. falciparum, diverging from a single FIKK in other Apicomplexa, indicating significant gene expansion and evolutionary adaptation.

Malaria, primarily caused by P. falciparum, affects over 200 million people annually and results in approximately 500,000 deaths, with increasing drug resistance posing a significant challenge to treatment.

The experimental work was primarily conducted at the Francis Crick Institute, with contributions from various research groups, including Université Laval in Canada.

Hugo Belda highlighted the importance of collaborative research across institutions to develop treatments that target multiple proteins and reduce the risk of drug resistance.