The dual role of sertraline: From antidepressant to antifungal drug with broad metabolic disruption

Abstract Sertraline, a selective serotonin reuptake inhibitor, is a widely used antidepressant. In recent decades, research has revealed its potential for drug repurposing, demonstrating various biological activities beyond psychiatric applications, including antifungal, antibacterial, antitumor, anthelmintic, and leishmanicidal effects. This review explores the antifungal potential of sertraline and its possible mechanisms of action against fungal cells, highlighting similarities with its effects in higher eukaryotes. We examine the effects of sertraline on (1) gene expression pathways, (2) lipid and carbohydrate metabolism, (3) membrane function, (4) stress response, and (5) alternative splicing modulation. Finally, we discuss future perspectives on the use of sertraline as an antifungal agent.