Influenza outbreaks cause pandemics in millions of people. The treatment of influenza remains a challenge due to significant genetic polymorphism in the influenza virus. Also, developing vaccines to protect against seasonal and pandemic influenza infections is constantly impeded. Thus, antibiotics are the only first line of defense against antigenically distinct strains or new subtypes of influenza viruses. Among several anti-influenza targets, the M2 protein of the influenza virus performs several activities. M2 protein is an ion channel that permits proton conductance through the virion envelope and the deacidification of the Golgi apparatus. Both these functions are critical for viral replication. Thus, targeting the M2 protein of the influenza virus is an essential target. Rimantadine and amantadine are two well-known drugs that act on the M2 protein. However, these drugs acquired resistance to influenza and thus are not recommended to treat influenza infections. This review discusses an overview of anti-influenza therapy, M2 ion channel functions, and its working principle. It also discusses the M2 structure and its role, and the change in the structure leads to mutant variants of influenza A virus. We also shed light on the recently identified compounds acting against wild-type and mutated M2 proteins of influenza virus A. These scaffolds could be an alternative to M2 inhibitors and be developed as antibiotics for treating influenza infections.

中文翻译：

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M2 离子通道阻滞剂对抗甲型流感病毒：最新进展和局限性


流感爆发导致数百万人流行。由于流感病毒显着的基因多态性，流感的治疗仍然是一个挑战。此外，开发预防季节性和大流行性流感感染的疫苗也不断受到阻碍。因此，抗生素是针对抗原不同的流感病毒株或新亚型的唯一第一道防线。在多个抗流感靶标中，流感病毒的 M2 蛋白发挥多种活性。 M2 蛋白是一种离子通道，允许质子传导通过病毒体包膜和高尔基体脱酸。这两种功能对于病毒复制都至关重要。因此，针对流感病毒的M2蛋白是一个重要的靶点。金刚乙胺和金刚烷胺是两种作用于 M2 蛋白的著名药物。然而，这些药物获得了对流感的耐药性，因此不推荐用于治疗流感感染。本文综述了抗流感治疗、M2 离子通道功能及其工作原理的概述。还讨论了M2结构及其作用，结构的改变导致了甲型流感病毒的突变变种。我们还阐明了最近发现的针对甲型流感病毒野生型和突变型 M2 蛋白的化合物。这些支架可以作为 M2 抑制剂的替代品，并可开发为治疗流感感染的抗生素。