Free Radical and Viral Infection: A Review from the Perspective of Ferroptosis

SIMPLE SUMMARY: Ferroptosis is an iron-catalyzed, oxidative form of cell death. It is accompanied by a large amount of iron accumulation and lipid peroxidation. Increasingly, studies have demonstrated that ferroptosis is closely associated with various organ injuries and degenerative pathologies, among others. This review aims to investigate the molecular mechanism between free radicals and ferroptosis in the viral infection state. This review also discusses the possibility of using ferroptosis inducers and inhibitors to treat viral diseases, providing some theoretical basis for studying the pathogenesis and prevention of viruses. ABSTRACT: Free radicals, including reactive oxygen species (ROS) and reactive nitrogen species (RNS), play critical roles in various physiological activities such as cell differentiation, apoptosis, and vascular tension when existing in cells at low levels. However, excessive amounts of free radicals are harmful, causing DNA damage, lipid peroxidation, protein degeneration, and abnormal cell death. Certain viral infections induce cells to produce excessive free radicals, which in multiple ways help the virus to replicate, mature, and exit. Iron is a necessary element for many intracellular enzymes, involved in both cellular activities and viral replication. Ferroptosis, a programmed cell death mode distinct from apoptosis, necrosis, and pyroptosis, is characterized by lipid peroxide accumulation and damage to the antioxidant system, affecting many cellular processes. Viral infection commonly manifests as decreased glutathione (GSH) content and down-regulated glutathione peroxidase 4 (GPX4) activity, similar to ferroptosis. Recent studies have suggested a possible relationship among free radicals, viral infections and ferroptosis. This review aims to elucidate the molecular mechanism linking free radicals and ferroptosis during viral infections and provide a new theoretical basis for studying viral pathogenesis and control.