Bioprospecting for Novel Heat Shock Protein Modulators: The New Frontier for Antimalarial Drug Discovery?

Abstract

Heat shock proteins are conserved molecules whose main role is to facilitate protein folding. However, they are also implicated in protein trafficking, protein assembly/disassembly, and functional maturation of proteins implicated in several biochemical pathways, including signal transduction. The role of heat shock proteins in the development of malaria parasites has recently become a subject of enormous interest. This is they do not only serve a cytoprotective role to ensure parasite survival but are implicated in the trafficking of several parasite proteins that are exported to the infected host red blood cell. Indeed, several heat shock proteins are also exported to the infected human red blood cell. In light of this, heat shock proteins along with other molecules are thought to modify the host cell, thus regulating the pathogenicity of malaria parasites. Even more important is their role in augmenting parasite resistance against antimalarial drugs. In light of the essential functions of several of these molecules in the development of malaria parasites, coupled with their role in antimalarial drug resistance, there is growing interest to target them as part of antimalarial drug discovery efforts. Several antimalarial compounds used so far originate from natural products. It is only logical that in our pursuit to identify small molecule inhibitors targeting heat shock proteins of malaria parasites, we turn to nature for answers and possible clues. In the current narrative, we focus attention on features of heat shock proteins of malaria parasites that make them amenable to targeting. In addition, we discuss various plant products that have been identified as sources of antimalarial compounds that target heat shock proteins. The current narrative seeks to inspire novel drug discovery experts, especially those working on natural compounds to focus on heat shock proteins as possible antimalarial targets. We further discuss the challenges of taking this route as part of our growing arsenal against malaria.

Keywords: Antimalarial; Bioprospecting; Chaperones; Drug resistance; Hsp; Natural compounds.