Mechanistic and Structural Insights into Oxidative Stress in Malaria and Anti-malarial Drug Metabolism

Abstract

Malaria is a devastating infectious disease affecting mostly tropical and sub-tropical regions. Owning to the emergence of resistance to the existing chemotherapy, the development of anti-malarial drugs as novel chemotherapeutics remains unavoidable. Malaria parasite, Plasmodium, experiences oxidative stress throughout its life cycle upon infection, and underlying redox metabolism is quite complex. Alterations in the redox homeostasis occur during host-pathogen interactions. Parasite is highly vulnerable to such alterations in redox homeostasis. To circumvent this, the parasites engage in an efficient redox system having protective roles towards the turbulence faced by the parasite. Targeting the redox system of malaria parasite is tempting in developing novel antimalarial drugs. On the other hand, oxidative stress, generated during anti-malarial drug metabolism, acts as a source of inhibition against progression of this outrageous parasite. This review aims to provide updated knowledge on redox networks of parasite and structural insights of redox system enzymes, underpinning the balance between antioxidant and pro-oxidant candidates throughout the host-parasite interactions. Furthermore, it also highlights the importance of reactive oxygen species generation during anti-malarial drug metabolism. This review summarises on the vulnerabilities of the malaria parasite due to oxidative stress and the potential cues towards development of the novel antimalarial drugs.