Plasmodium falciparum Transferases as Potential Antimalarial Targets:

Abstract

The current report describes the experience that the author gained during her 11 months of internship placement at Indonesia International Institute for Life Sciences (i3L). The internship was organized by Ms. Elizabeth Sidhartha, B.Sc., M.Sc. (a Biomedicine faculty) and was conducted online. The goal of this internship is to produce a systematic review discussing the potential of Plasmodium falciparum (Pf) blood-stage proteins as new antimalarial targets in recognition of the fact that Pf has developed resistance to several drugs on the market. Pf transferases were specifically addressed and analyzed in the systematic review due to their involvement in various cellular processes of parasites. Among 1,109 articles collected from three academic research databases, only 20 articles met the research criteria and were eligible for analysis. From these articles, 11 types of drug-interacting transferases were identified and they were classified into three functional categories, including regulation of metabolism (3 transferases), epigenetic regulation (3 transferases), and lipid biosynthesis and protein lipidation (5 transferases). These functions are found to be closely associated with cell cycle progression, host invasion, and virulence gene expression of parasites. Therefore, interference with their enzymatic activity with small inhibitors reduces the ability of the parasite to transmit, grow, and survive during the intraerythrocytic stage. This study was also able to identify several promising drugs under optimization and repositioning to target Pf transferases. Taken together, this systematic review provides the first analysis of the biology and function of drug-interacting Pf transferases as novel antimalarial targets for combating multidrug-resistant strains.