Mutations in influenza virus neuraminidase (NA) can lead to viral resistance to NA inhibitors (NAIs). To update global influenza NA mutations and resistance to NAIs, we investigated epidemic information from global regions for NAIs-resistant influenza strains and analyzed their NA mutations. Drug-resistant mutations in NA, especially new mutations occurred in 2016-2024, were updated. The H274Y mutation in N1, a major contributor to NAI resistance, peaked in 2008, significantly impacting public health in countries like Japan and the USA. Three main mechanisms of NAI resistance were identified: catalytic site mutations, structural hindrance, and monomer stability changes. Although global resistance rates of H1N1pdm09, H3N2, and influenza B have remained stable at around 1%, sporadic emergence of resistant strains highlights the need for continued vigilance. The evolution of drug-resistant, transmissible strains through compensatory mutations underscores the urgency of new antiviral strategies. Strengthening global surveillance and adjusting public health policies, such as improving vaccine coverage and prudent antiviral use, remain essential to mitigating future risks.

中文翻译：

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流感神经氨酸酶突变和对神经氨酸酶抑制剂的耐药性。


流感病毒神经氨酸酶 （NA） 突变可导致病毒对 NA 抑制剂 （NAI） 的耐药性。为了更新全球流感 NA 突变和对 NAI 的耐药性，我们调查了全球地区对 NAIs 耐药流感毒株的流行信息并分析了它们的 NA 突变。更新了 NA 中的耐药突变，尤其是 2016-2024 年发生的新突变。N1 中的 H274Y 突变是导致 NAI 耐药性的主要因素，在 2008 年达到顶峰，对日本和美国等国家的公共卫生产生了重大影响。确定了 NAI 耐药的 3 种主要机制：催化位点突变、结构阻碍和单体稳定性变化。尽管 H1N1pdm09、H3N2 和乙型流感的全球耐药率一直稳定在 1% 左右，但零星出现的耐药菌株凸显了持续保持警惕的必要性。耐药、可传播菌株通过代偿性突变的进化强调了新抗病毒策略的紧迫性。加强全球监测和调整公共卫生政策，例如提高疫苗覆盖率和谨慎使用抗病毒药物，对于减轻未来风险仍然至关重要。