Revisiting Glutathione Transferases of Plasmodium as Potential Targets for Coadjuvant Therapies and the Development of New Antimalarials

Malaria remains a major global health problem, especially in low- and mid-income countries where Plasmodium parasites are commonly endemic. Despite the significant number of available drugs to treat the disease, some aspects, such as increasing resistance to frontline antimalarials, inefficient treatment of asymptomatic carriers and treatment inadequacy for certain vulnerable groups, are jeopardizing control measures, justifying the need for therapeutic targets driving the discovery of new compounds. In this context, glutathione transferases, which are essential for redox metabolism and detoxification of heme in the asexual blood stages of Plasmodium parasites, have emerged as promising targets more than two decades ago, but have been deprioritized due to significant gaps in research. This review aims to synthesize current biochemical, structural, genetic, and transcriptomic evidence on Plasmodium glutathione S-transferases and evaluate their role in parasite physiology across the life cycle while revising their potential for drug targeting using suggested guidelines for target candidate profiling and prioritization.