Kexin Wang, Yuepeng Li, Xiaohong Chen, Zifeng Yang
Influenza virus infection remains a leading cause of acute respiratory illness worldwide, with increasing resistance to conventional antiviral therapies highlighting the need for novel therapeutic strategies. This review introduces the concept of metabolizeaccretion, a self-reinforcing pathological cascade driven by metabolic reprogramming and characterized by three progressive stages: trigger, amplification, and persistence. During influenza infection, viral-induced alterations in glucose, lipid, amino acid, and purine metabolism lead to the aberrant accumulation of metabolic intermediates, which are associated with disrupted cellular energy homeostasis, altered inflammatory and immune responses, and potential epigenetic modifications that may stabilize pathological phenotypes. These processes collectively effect viral replication, immune evasion, and progression to severe respiratory damage. We further discuss potential therapeutic interventions targeting key metabolic enzymes, accumulated metabolites, gene expression regulation, and specific receptors to disrupt metabolizeaccretion. Finally, we emphasize the importance of multi-target approaches and precision medicine strategies to address metabolic heterogeneity in lung microenvironments, offering new insights for the treatment and management of influenza and related respiratory diseases.