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.
Highlights
Malaria is a major global parasitic disease and a cause of enormous mortality and morbidity
This review focuses on the potential of P. falciparum serine proteases as antimalarial drug targets
Given its essentiality for parasite blood and liver stages, proteolytic activity on multiple parasite proteins, and role in egress and invasion, PfSUB1 qualifies as an attractive antimalarial drug target
Summary
Malaria caused by protozoan parasite Plasmodium is a major global parasitic disease [1]. Chloroquine resistance prompted many countries to adopt sulfadoxine-pyrimethamine (SP) as the first-line antimalarial but resistant P. falciparum populations were selected quickly in Africa, Southeast Asia, and South America. It was abandoned after only 5 years of use in Southeast Asia [5, 6]. The artemisinins are potent and rapidly acting antimalarials derived from the Chinese sweet wormwood plant, Artemisia annua [7, 8]. Despite the effectiveness of ACTs, use of artemisinin monotherapy resulted in emergence of drug-resistant P. falciparum parasites in Cambodia-Thailand border region [11, 12]. Despite the availability of antimalarials for both treatment and prophylaxis, the spread of resistance and paucity of more antimalarials warrants the need for identification of new drug targets and development of novel drugs
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