The Potential Role of Selenoproteins in Modulating Malaria Parasite Resistance to Artemisinin-based Combination Therapies (ACTs) in Africa

Abstract

This review synthesises current knowledge on the structure, function, and expression of Plasmodium falciparum selenoproteins, focusing on thioredoxin reductase (PfTrxR), and their role in mitigating artemisinin-induced oxidative damage. Resistance to artemisinin-based combination therapies (ACTs), the cornerstone of malaria treatment, threatens global health, particularly in Africa, where Plasmodium falciparum predominates. Although the mechanisms of artemisinin resistance remain incompletely elucidated, selenoproteins —critical for redox homeostasis —are implicated in parasite survival under drug-induced oxidative stress. By integrating molecular, biochemical, and clinical data, we highlight that targeting selenoproteins, which differ structurally from their human counterparts, is a promising strategy for overcoming ACT resistance. Proposed therapeutic approaches, such as selective inhibitors like auranofin, could enhance ACT efficacy by disrupting parasite redox balance. This approach holds significant potential for improving malaria treatment outcomes in endemic regions, addressing a critical public health challenge.