Influenza virus is a kind of respiratory pathogen with high morbidity and mortality, which still threatens human health. Existing anti-influenza drugs have various limitations, such as the inability to alleviate body injury and side effects. There remains an urgent need to develop a novel antiviral drug to efficiently inhibit viral infection while avoiding body injury. A series of 2-aminoindole derivatives were synthesized via the TMSOTf-catalyzed reactions of N-arylynamides with sulfilimines and evaluated for their anti-influenza virus activity. The experimental results showed that 2-aminoindole 3h had significant antiviral activity (EC50 = 8.37 ± 0.65 μM) and the lowest cytotoxicity (CC50 = 669.26 ± 11.42 μM) in vitro. 2-Aminoindole 3h could inhibit viral replication by effectively binding to RNA-dependent RNA polymerase (RdRp), and could also directly target host cells to inhibit cytokine storms and apoptosis induced by viral infection, thereby improving host cell survival rate. In addition, viral load and organ injury in the lung tissue of infected mice were effectively reduced by 2-aminoindole 3h with satisfactory biosafety. These findings highlight the potential of a valuable therapeutic option against influenza infection while also laying the foundation for further research and development in this area.

中文翻译：

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2-氨基吲哚衍生物抗甲型流感病毒体外/体内合成及药效学评价


流感病毒是一类发病率和死亡率高的呼吸道病原体，至今仍威胁着人类健康。现有的抗流感药物有各种局限性，例如无法减轻身体损伤和副作用。仍然迫切需要开发一种新型抗病毒药物，以有效抑制病毒感染，同时避免身体损伤。通过 N-芳基酰胺与硫胺的 TMSOTf 催化反应合成了一系列 2-氨基吲哚衍生物，并评价了它们的抗流感病毒活性。实验结果表明，2-氨基吲哚 3h 在体外具有显著的抗病毒活性 （EC50 = 8.37 ± 0.65 μM） 和最低的细胞毒性 （CC50 = 669.26 ± 11.42 μM）。2-氨基吲哚 3h 可通过有效结合 RNA 依赖性 RNA 聚合酶 （RdRp） 来抑制病毒复制，还可以直接靶向宿主细胞抑制病毒感染诱导的细胞因子风暴和细胞凋亡，从而提高宿主细胞存活率。此外，2-氨基吲哚 3 h 有效降低了感染小鼠肺组织中的病毒载量和器官损伤，生物安全性令人满意。这些发现凸显了针对流感感染的宝贵治疗选择的潜力，同时也为该领域的进一步研究和开发奠定了基础。