Viroporins: emerging viral infection mechanisms and therapeutic targets.

Viroporins, virus-encoded small hydrophobic proteins, are involved in critical steps of viral infections by modulating ion homeostasis, disrupting host membrane integrity, and orchestrating key stages of the virus life cycle-from entry and replication to release. Beyond facilitating viral propagation, these pore-forming proteins exacerbate pathogenesis by disrupting cellular ion homeostasis and triggering proinflammatory responses through NLRP3 inflammasome activation. Their dual role in viral fitness and immunopathology positions viroporins as promising antiviral targets for dual-action therapeutics: suppressing replication while attenuating inflammation. However, structural constraints and low immunogenicity hinder vaccine development targeting conserved viroporin domains. This review summarizes recent advances in viroporin mechanisms, highlights progress in viroporin-targeted drug and vaccine design, and discusses persistent challenges. Furthermore, the emerging technologies (e.g., AI-driven structural prediction and nanodelivery systems) are expected to significantly accelerate the development of next-generation viroporin-targeted therapeutics and vaccines. Taken together, this review underscores the critical roles of viroporins in viral pathogenesis, emphasizing their potential as promising targets for the prevention and control of viral diseases.