Bonomini Anna, Mercorelli Beatrice, Loregian Arianna
Department of Molecular Medicine, University of Padua, Padua, Italy.
Microbiology and Virology Unit, Padua University Hospital, Padua, Italy.
Cell Mol Life Sci. 2025 Feb 13;82(1):75. doi: 10.1007/s00018-025-05611-1.
Influenza viruses still represent a great concern for Public Health by causing yearly seasonal epidemics and occasionally worldwide pandemics. Moreover, spillover events at the animal-human interface are becoming more frequent nowadays, also involving animal species not previously found as reservoirs. To restrict the effects of influenza virus epidemics, especially in at-risk population, and to prepare a drug arsenal for possible future pandemics, researchers worldwide have been working on the development of antiviral strategies since the 80's of the last century. One of the main obstacles is the considerable genomic variability of influenza viruses, which constantly poses the issues of drug-resistance emergence and immune evasion. This review summarizes the approved therapeutics for clinical management of influenza, promising new anti-flu compounds and monoclonal antibodies currently undergoing clinical evaluation, and molecules with efficacy against influenza virus in preclinical studies. Moreover, we discuss some innovative anti-influenza therapeutic approaches such as combination therapies and targeted protein degradation. Given the limited number of drugs approved for influenza treatment, there is a still strong need for novel potent anti-influenza drugs endowed with a high barrier to drug resistance and broad-spectrum activity against influenza viruses of animal origin that may be responsible of future large outbreaks and pandemics.
流感病毒每年引发季节性流行，偶尔还会导致全球大流行，仍然是公共卫生领域的重大关切。此外，如今动物与人类之间的病毒溢出事件越来越频繁，涉及的动物物种也不再局限于以往发现的宿主。为了限制流感病毒流行的影响，特别是对高危人群的影响，并为未来可能出现的大流行储备药物，自上世纪80年代以来，世界各地的研究人员一直致力于开发抗病毒策略。主要障碍之一是流感病毒基因组的显著变异性，这不断引发耐药性出现和免疫逃逸问题。本综述总结了已批准用于流感临床治疗的药物、有望用于治疗流感的新化合物和目前正在进行临床评估的单克隆抗体，以及在临床前研究中对流感病毒有效的分子。此外，我们还讨论了一些创新的抗流感治疗方法，如联合疗法和靶向蛋白降解。鉴于已批准用于流感治疗的药物数量有限，仍然迫切需要新型强效抗流感药物，这些药物对耐药性具有高屏障作用，并且对可能导致未来大规模疫情和大流行的动物源流感病毒具有广谱活性。
