Recent advances in identification of potential drug targets and development of novel drugs in parasitic diseases. Part IV. Plasmodium spp.

Abstract

In the last two decades, transporters attracted much attention in identification of potential drug targets against intracellular protozoa. Several membrane molecules exhibit essential roles in trafficking pathways for nutrients, essential enzymes and virulence factors. In this context, P. falciparum possesses a complex of genomic plasticity-encoding transporters with high potentiality for aneuploidy, and gene expression modulation in response to drug exposure. Therefore, it is able to undergo gene mutations in enzymes controlling drug uptake, and evade host immune response by antigenic variations as well. The genetic mechanism of antimalarial drug resistance arises early with monotherapy using fast-acting drugs or a single targeting drug. Accordingly, combined therapy acting on multiple targets would decrease the emergence of drug resistance. Evolutionary technology on genetic approach enabled researchers to identify and propose novel Plasmodium drug targets. The main objective of this part is to review potential drug targets for apicomplexans and discuss recent approaches in identifying Plasmodium targets, as well as advances in the design and development of novel antimalarial drugs.