A comprehension and systematic insight into the interaction between ferroptosis and virus infection: The implications of mechanisms and strategies

Ferroptosis is a novel form of iron-dependent programmed cell death characterized by iron metabolic derangement, an abnormal antioxidant system, and lipid peroxidation. Emerging evidence revealed that viruses modulate ferroptosis to facilitate their replication, dissemination, and pathogenesis, thereby promoting infection or achieving immune evasion by hijacking the host's iron metabolism. However, the interplay between ferroptosis and virus infections remains to be elucidated. This review comprehensively summarizes the core mechanisms of ferroptosis, including iron homeostasis, the system Xc-/GPX4 pathway, the FSP1/CoQ10 pathway, lipid peroxidation, and their essential roles were discussed in ferroptosis. We highlighted the relationship between the core mechanisms of ferroptosis and virus infection. Furthermore, we revealed the underlying pathogenic mechanisms of viral infections and the prospective applications targeting ferroptosis. This article is conducive to deepening our understanding of the regulatory mechanism of ferroptosis, unraveling the potential therapeutic intervention and pharmacological direction for the development of innovative ferroptosis-dependent antiviral agents.