Plasmodium falciparum Transketolase as a Drug Target in Malaria: A Review of Current Research and Future Perspectives

Abstract

Malaria is a severe infectious disease caused by Plasmodium species, primarily Plasmodium falciparum, which accounts for the most deaths globally. Africa bears the heaviest malaria burden, with countries like Nigeria, Congo, and Mozambique contributing to a significant percentage of global cases. It is transmitted through the bite of an infected female Anopheles mosquito. The fight against malaria has been challenged by the emergence of resistance to most antimalarial drugs, including Artemisinin-based Combination Therapies (ACTs). This highlights the urgent need for novel drug targets. Transketolase (Tk), a key enzyme in the pentose phosphate pathway (PPP) non-oxidative branch, plays a vital role in cellular metabolism and has been identified to support parasite survival. Plasmodium falciparum transketolase (PfTk) has been identified as an emerging drug target due to its essential role in the parasite's metabolism and low structural homology with human transketolase (HTk). This review aims to provide an overview of PfTk as a potential anti-malarial drug target and to highlight the key research direction for future drug development. It examines the current research on PfTk as a therapeutic target, focusing on its biochemical properties, structural and functional characteristics, and potential inhibitors' development as a therapeutic strategy while exploring future perspectives.