The neuraminidase (NA) of influenza A and B viruses plays a distinct role in viral replication and has a highly conserved catalytic site. Numerous sialic (neuraminic) acid analogs that competitively bind to the NA active site and potently inhibit enzyme activity have been synthesized and tested. Four NA inhibitors are now licensed in various parts of the world (zanamivir, oseltamivir, peramivir, and laninamivir) to treat influenza A and B infections. NA changes, naturally occurring or acquired under selective pressure, have been shown to reduce drug binding, thereby affecting the effectiveness of NA inhibitors. Drug resistance and other drawbacks have prompted the search for the next-generation NA-targeting therapeutics. One of the promising approaches is the identification of monoclonal antibodies (mAbs) targeting the conserved NA epitopes. Anti-NA mAbs demonstrate Fab-based antiviral activity supplemented with Fc-mediated immune effector functions. Antiviral Fc-conjugates offer another cutting-edge strategy that is based on a multimodal mechanism of action. These novel antiviral agents are composed of a small-molecule NA inhibitor and an Fc-region that simultaneously engages the immune system. The significant advancements made in recent years further support the value of NA as an attractive target for the antiviral development.

中文翻译：

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针对神经氨酸酶的抗病毒药物

甲型和乙型流感病毒的神经氨酸酶 (NA) 在病毒复制中起着独特的作用，并具有高度保守的催化位点。已经合成和测试了许多竞争性结合 NA 活性位点并有效抑制酶活性的唾液酸（神经氨酸）酸类似物。四种 NA 抑制剂现已在世界各地获得许可（扎那米韦、奥司他韦、帕拉米韦和拉尼米韦）用于治疗甲型和乙型流感感染。在选择性压力下自然发生或获得的 NA 变化已被证明会降低药物结合，从而影响 NA 抑制剂的有效性。耐药性和其他缺点促使人们寻找下一代 NA 靶向疗法。有希望的方法之一是鉴定靶向保守的 NA 表位的单克隆抗体 (mAb)。抗 NA mAb 表现出基于 Fab 的抗病毒活性，并辅以 Fc 介导的免疫效应功能。抗病毒 Fc 偶联物提供了另一种基于多模式作用机制的前沿策略。这些新型抗病毒药物由小分子 NA 抑制剂和同时参与免疫系统的 Fc 区组成。近年来取得的重大进展进一步支持了 NA 作为抗病毒开发的有吸引力的目标的价值。