Serine Proteases of Malaria Parasite Plasmodium falciparum: Potential as Antimalarial Drug Targets

Abstract

Malaria is a major global parasitic disease and a cause of enormous mortality and morbidity. Widespread drug resistance against currently available antimalarials warrants the identification of novel drug targets and development of new drugs. Malarial proteases are a group of molecules that serve as potential drug targets because of their essentiality for parasite life cycle stages and feasibility of designing specific inhibitors against them. Proteases belonging to various mechanistic classes are found in P. falciparum, of which serine proteases are of particular interest due to their involvement in parasite-specific processes of egress and invasion. In P. falciparum, a number of serine proteases belonging to chymotrypsin, subtilisin, and rhomboid clans are found. This review focuses on the potential of P. falciparum serine proteases as antimalarial drug targets.

Figure 1

Role of serine proteases at asexual blood stages (a) and liver stages of Plasmodium falciparum (b). Subtilisin-like proteases are essential for merozoite invasion and egress in blood stages, liver stage schizont development and subsequent liver stage merozoite egress. Rhomboid protease activities are supposed to be involved in invasion of RBC and liver.