Abstract

Influenza A virus pandemics still remain a threat to global health. One class of antiviral drugs, namely, inhibitors of the specific viral enzyme neuraminidase, is predominantly used in the fight against these pandemics. These antivirals include zanamivir (Relenza™) and oseltamivir (Tamiflu™). The viral resistance to this class of compounds steadily increases. The M2 proton channel of influenza A virus is an alternative clinically proven target for antiviral therapy. However, many circulating virus strains bear amino acid mutations in the M2 protein, causing resistance to drugs of the adamantane series, M2 blockers, such as rimantadine and amantadine. Consequently, inhibitors targeting mutants of the M2 channel are urgently needed for public biosafety and health. This review is devoted to structural-functional interactions used in practice and mediated by the action of experimental drugs on the protein target, the transmembrane domain of the influenza virus M2 proton channel. An analysis of the experimental and model structural data available in open access is presented.

中文翻译：

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甲型流感病毒 M2 质子通道与金刚烷类抗病毒药物相互作用的结构基础

摘要

甲型流感病毒大流行仍然对全球健康构成威胁。一类抗病毒药物，即特定病毒酶神经氨酸酶的抑制剂，主要用于对抗这些流行病。这些抗病毒药物包括扎那米韦 (Relenza™) 和奥司他韦 (Tamiflu™)。病毒对此类化合物的耐药性稳步增强。甲型流感病毒的 M2 质子通道是临床证明的抗病毒治疗的替代靶点。然而，许多流行病毒株的 M2 蛋白存在氨基酸突变，导致对金刚烷系列药物、M2 阻滞剂（如金刚乙胺和金刚烷胺）产生耐药性。因此，为了公共生物安全和健康，迫切需要针对 M2 通道突变体的抑制剂。这篇综述致力于实践中使用的结构-功能相互作用，并由实验药物对蛋白质靶标（流感病毒 M2 质子通道的跨膜结构域）的作用介导。对开放获取中可用的实验和模型结构数据进行了分析。