Qu Yuxin, Li Jiaqi, Deng Hao, Wang Yanjin, Li Lian-Feng, Xia Bingqing, Li Yongfeng, Qiu Hua-Ji, Li Su
State Key Laboratory for Animal Disease Control and Prevention, Harbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Harbin, China.
CAS Key Laboratory of Receptor Research, State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, China.
J Virol. 2025 Sep 23;99(9):e0103825. doi: 10.1128/jvi.01038-25. Epub 2025 Sep 2.
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.
病毒孔蛋白是病毒编码的小疏水蛋白，通过调节离子稳态、破坏宿主膜完整性以及协调病毒生命周期的关键阶段（从进入和复制到释放），参与病毒感染的关键步骤。除了促进病毒传播外，这些成孔蛋白还通过破坏细胞离子稳态和通过NLRP3炎性小体激活触发促炎反应，加剧发病机制。它们在病毒适应性和免疫病理学中的双重作用使病毒孔蛋白成为双作用疗法有前景的抗病毒靶点：抑制复制同时减轻炎症。然而，结构限制和低免疫原性阻碍了针对保守病毒孔蛋白结构域的疫苗开发。本综述总结了病毒孔蛋白机制的最新进展，强调了针对病毒孔蛋白的药物和疫苗设计的进展，并讨论了持续存在的挑战。此外，新兴技术（如人工智能驱动的结构预测和纳米递送系统）有望显著加速下一代针对病毒孔蛋白的治疗药物和疫苗的开发。综上所述，本综述强调了病毒孔蛋白在病毒发病机制中的关键作用，强调了它们作为预防和控制病毒疾病有前景的靶点的潜力。
