1.Cytoadherence and Severe Malaria
Alister G Craig ; Mohd Fadzli Mustaffa Khairul ; Pradeep R Patil
Malaysian Journal of Medical Sciences 2012;19(2):5-18
Malaria is a disease that causes enormous human morbidity and mortality. One feature of mature Plasmodium falciparum-infected erythrocytes leading to the development of severe malaria is thought to be cytoadherence and blockage of the microvasculature. Therefore, an understanding of mechanisms that mediate parasite adhesion leading to malaria pathology is needed to yield new treatments for malaria. However, to date, cytoadherence-associated pathology is still under debate. Is cytoadherence needed to develop severe malaria? This review will discuss the available information on associations of cytoadherence with the development of severe malaria.
2. ATP gatekeeper of Plasmodium protein kinase may provide the opportunity to develop selective antimalarial drugs with multiple targets
Fauze MAHMUD ; Khairul Fadzli MUSTAFFA ; Chiuan LEOW ; Ngit Shin LAI ; Fauze MAHMUD ; Ping LEE ; Habibah WAHAB ; Azhar RASUL
Asian Pacific Journal of Tropical Medicine 2020;13(8):350-357
Malaria is one of the most devastating infectious diseases that caused millions of clinical cases annually despite decades of prevention efforts. Recent cases of Plasmodium falciparum resistance against the only remaining class of effective antimalarial (artemisinin) in South East Asia may soon pose a significant threat. Hence, the identification of new antimalarial compounds with a novel mode of action is necessary to curb this problem. Protein kinase has been implicated as a valid target for drug development in diseases such as cancer and diabetes in humans. A similar approach is now recognized for the treatment of protozoan-related disease including malaria. Few Plasmodium protein kinases that are not only crucial for their survival but also have unique structural features have been identified as a potential target for drug development. In this review, studies on antimalarial drug development exploiting the size of Plasmodium protein kinase ATP gatekeeper over the past 15 years are mainly discussed. The ATP-binding site of Plasmodium protein kinases such as Pf CDPK1, Pf CDPK4, Pf PKG, Pf PK7, and Pf PI4K showed great potential for selective and multi-target inhibitions owing to their smaller or unique ATP-gatekeeper amino acid subunits compared to that of human protein kinase. Hence it is a feasible solution to identify a new class of active antimalarial agents with a novel mode of action and longer clinical life-span.