The oxidative stress paradigm in arbovirus infections: mechanisms and therapeutic insights.

Abstract

<h4>Background</h4>Arbovirus infections impose a substantial global health burden, further complicated by their ability to induce oxidative stress through excessive generation of reactive oxygen species (ROS). This oxidative stress triggers a cascade that enhances viral replication and dysregulates immune responses, ultimately exacerbating disease pathology.<h4>Objective</h4>In this review, we delineate the molecular pathways through which arbovirus-induced ROS activate NF-κB signalling, impair mitochondrial function, and alter the expression of key antioxidant enzymes (superoxide dismutase, catalase, and glutathione peroxidase), culminating in inflammatory tissue damage.<h4>Discussions</h4><i>In vitro</i> studies demonstrate that various alkaloids and polyphenols reduce viral load, while N-acetylcysteine has shown the ability to attenuate inflammation and reduce viral titres across both <i>in vitro</i> and <i>in vivo</i> models. Despite these advances, translation to clinical practice is constrained by limited compound bioavailability, variable pharmacokinetics, optimal timing windows, and a lack of standardized redox assays.<h4>Conclusion</h4>We propose that targeted redox-modulating strategies, such as integrating genomic and metabolomic profiling, activating Nrf2 pathways, and incorporating advanced imaging techniques, warrant systematic evaluation using rigorous <i>in vivo</i> models and clinical trials. Defining optimal redox-directed interventions has the potential to catalyse the discovery of novel therapeutics that disrupt pro-viral oxidative pathways and improve outcomes in arboviral disease.