Abstract:
Apicomplexan parasites have challenged researchers for nearly a century. A major challenge to developing efficient treatments
and vaccines is the parasite’s ability to change its cellular and molecular makeup to develop intracellular and extracellular
niches in its hosts. Ca2þ signaling is an important messenger for the egress of the malaria parasite from the infected erythrocyte,
gametogenesis, ookinete motility in the mosquito, and sporozoite invasion of mammalian hepatocytes. Calciumdependent
protein kinases (CDPKs) have crucial functions in calcium signaling at various stages of the parasite’s life cycle; this
therefore makes them attractive drug targets against malaria. Here, we summarize the functions of the various CDPK isoforms
in relation to the malaria life cycle by emphasizing the molecular mechanism of developmental progression within host tissues.
We also discuss the current development of anti-malarial drugs, such as how specific bumped kinase inhibitors (BKIs) for
parasite CDPKs have been shown to reduce infection in Toxoplasma gondii, Cryptosporidium parvum, and Plasmodium falciparum.
Our suggested combinations of BKIs, artemisinin derivatives with peroxide bridge, and inhibitors on the Ca(2þ)-ATPase
PfATP6 as a potential target should be inspected further as a treatment against malaria.
