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

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.

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.

In vitro 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 in vitro and in vivo 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.

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 in vivo 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.