Heat Shock Proteins as Targets for Novel Antimalarial Drug Discovery.

Abstract

Plasmodium falciparum, the parasitic agent that is responsible for a severe and dangerous form of human malaria, has a history of long years of cohabitation with human beings with attendant negative consequences. While there have been some gains in the fight against malaria through the application of various control measures and the use of chemotherapeutic agents, and despite the global decline in malaria cases and associated deaths, the continual search for new and effective therapeutic agents is key to achieving sustainable development goals. An important parasite survival strategy, which is also of serious concern to the scientific community, is the rate at which the parasites continually develop resistance to drugs. Among the key players in the parasite's ability to develop resistance, maintain cellular integrity, and survives within an unusual environment of the red blood cells are the molecular chaperones of the heat shock proteins (HSP) family. HSPs constitute a novel avenue for antimalarial drug discovery and by exploring their ubiquitous nature and multifunctional activities, they may be suitable targets for the discovery of multi-targets antimalarial drugs, needed to fight incessant drug resistance. In this chapter, features of selected families of plasmodial HSPs that can be exploited in drug discovery are presented. Also, known applications of HSPs in small molecule screening, their potential usefulness in high throughput drug screening, as well as possible challenges are highlighted.