首页> 外文期刊>The Journal of Antibiotics: An International Journal >Azithromycin, a 15-membered macrolide antibiotic, inhibits influenza A(H1N1)pdm09 virus infection by interfering with virus internalization process
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Azithromycin, a 15-membered macrolide antibiotic, inhibits influenza A(H1N1)pdm09 virus infection by interfering with virus internalization process

机译:阿奇霉素,一种15元大环内酯抗生素,通过干扰病毒内化过程来抑制流感A(H1N1)PDM09病毒感染

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摘要

The pandemic influenza 2009 (A(H1N1)pdm09) virus currently causes seasonal and annual epidemic outbreaks. The widespread use of anti-influenza drugs such as neuraminidase and matrix protein 2 (M2) channel inhibitors has resulted in the emergence of drug-resistant influenza viruses. In this study, we aimed to determine the anti-influenza A(H1N1)pdm09 virus activity of azithromycin, a re-positioned macrolide antibiotic with potential as a new anti-influenza candidate, and to elucidate its underlying mechanisms of action. We performed in vitro and in vivo studies to address this. Our in vitro approaches indicated that progeny virus replication was remarkably inhibited by treating viruses with azithromycin before infection; however, azithromycin administration after infection did not affect this process. We next investigated the steps inhibited by azithromycin during virus invasion. Azithromycin did not affect attachment of viruses onto the cell surface, but blocked internalization into host cells during the early phase of infection. We further demonstrated that azithromycin targeted newly budded progeny virus from the host cells and inactivated their endocytic activity. This unique inhibitory mechanism has not been observed for other anti-influenza drugs, indicating the potential activity of azithromycin before and after influenza virus infection. Considering these in vitro observations, we administered azithromycin intranasally to mice infected with A(H1N1)pdm09 virus. Single intranasal azithromycin treatment successfully reduced viral load in the lungs and relieved hypothermia, which was induced by infection. Our findings indicate the possibility that azithromycin could be an effective macrolide for the treatment of human influenza.
机译:大流行性流感2009(A(H1N1)PDM09)病毒目前导致季节性和年度流行病爆发。抗流感药物如神氨酸酶和基质蛋白2(M2)通道抑制剂的广泛使用导致耐药性流感病毒的出现。在这项研究中,我们旨在确定阿奇霉素的抗流感A(H1N1)PDM09病毒活性,一种重新定位的大环内酯抗生素,其具有新的抗流感候选,并阐明其基础的行动机制。我们在体外进行,体内研究以解决这个问题。我们的体外方法表明,通过在感染前用氮霉素治疗病毒显着抑制后代病毒复制;然而,感染后的阿奇霉素给药不影响这一过程。我们接下来研究了在病毒侵袭过程中由阿奇霉素抑制的步骤。阿奇霉素不影响病毒的附着在细胞表面上,但在感染的早期阶段期间阻止内化到宿主细胞中。我们进一步证明阿奇霉素从宿主细胞靶向新芽的后代病毒并灭活它们的内吞活性。对于其他抗流感药物,尚未观察到这种独特的抑制机制,表明流感病毒感染前后阿奇霉素的潜在活动。考虑到这些体外观察,我们鼻内给予阿奇霉素到感染的小鼠(H1N1)PDM09病毒。单一鼻内氮杂霉素治疗成功降低了肺中的病毒载量并减轻了抑制的低温,其被感染诱导。我们的研究结果表明阿奇霉素可以是用于治疗人流感的有效大环内酯的可能性。

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    Teikyo Univ Dept Hlth Protect Grad Sch Med Itabashi Ku Kaga 2-11-1 Tokyo 1738605 Japan;

    Teikyo Univ Dept Hlth Protect Grad Sch Med Itabashi Ku Kaga 2-11-1 Tokyo 1738605 Japan;

    Kitasato Univ Kitasato Inst Life Sci Minato Ku Shirokane 5-9-1 Tokyo 1088641 Japan;

    Teikyo Univ Dept Hlth Protect Grad Sch Med Itabashi Ku Kaga 2-11-1 Tokyo 1738605 Japan;

    Kitasato Univ Kitasato Inst Life Sci Minato Ku Shirokane 5-9-1 Tokyo 1088641 Japan;

    Kitasato Univ Kitasato Inst Life Sci Minato Ku Shirokane 5-9-1 Tokyo 1088641 Japan;

    Teikyo Univ Asia Int Inst Infect Dis Control ADC Itabashi Ku Kaga 2-11-1 Tokyo 1738605 Japan;

    Teikyo Univ Asia Int Inst Infect Dis Control ADC Itabashi Ku Kaga 2-11-1 Tokyo 1738605 Japan;

    Teikyo Univ Asia Int Inst Infect Dis Control ADC Itabashi Ku Kaga 2-11-1 Tokyo 1738605 Japan;

    Kitasato Univ Kitasato Inst Life Sci Minato Ku Shirokane 5-9-1 Tokyo 1088641 Japan;

    Kitasato Univ Kitasato Inst Life Sci Minato Ku Shirokane 5-9-1 Tokyo 1088641 Japan;

    Kitasato Univ Kitasato Inst Life Sci Minato Ku Shirokane 5-9-1 Tokyo 1088641 Japan;

    Teikyo Hosp Univ Pediat Dept Itabashi Ku Kaga 2-11-1 Tokyo 1738605 Japan;

    Teikyo Hosp Univ Pediat Dept Itabashi Ku Kaga 2-11-1 Tokyo 1738605 Japan;

    Teikyo Univ Dept Hlth Protect Grad Sch Med Itabashi Ku Kaga 2-11-1 Tokyo 1738605 Japan;

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