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首页> 外文期刊>Nature >Small molecule inhibitors reveal Niemann-Pick C1 is essential for Ebola virus infection
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Small molecule inhibitors reveal Niemann-Pick C1 is essential for Ebola virus infection

机译：小分子抑制剂显示Niemann-Pick C1对埃博拉病毒感染至关重要

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摘要

Ebola virus (EboV) is a highly pathogenic enveloped virus that causes outbreaks of zoonotic infection in Africa. The clinical symptoms are manifestations of the massive production of pro-inflammatory cyto-kines in response to infection1 and in many outbreaks, mortality exceeds 75%. The unpredictable onset, ease of transmission, rapid progression of disease, high mortality and lack of effective vaccine or therapy have created a high level of public concern about EboV2. Here we report the identification of a novel benzylpiperazine ada-mantane diamide-derived compound that inhibits EboV infection. Using mutant cell lines and informative derivatives of the lead compound, we show that the target of the inhibitor is the endosomal membrane protein Niemann-Pick Cl (NPC1).
机译：埃博拉病毒（EboV）是一种高致病性包膜病毒，可导致非洲爆发人畜共患病感染。临床症状是对感染1大量产生促炎性细胞因子的表现1，在许多暴发中，死亡率超过75％。 EboV2的不可预测的发作，易传播，疾病的快速发展，高死亡率以及缺乏有效的疫苗或治疗方法引起了公众的高度关注。在这里，我们报告鉴定抑制EboV感染的新型苄基哌嗪ada-mantane二酰胺衍生的化合物。使用突变细胞系和前导化合物的信息丰富的衍生物，我们表明抑制剂的靶标是内体膜蛋白Niemann-Pick Cl（NPC1）。

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  • 来源
    《Nature》 |2011年第7364期|p.344-348|共5页
  • 作者

    Marceline Coté; John Misasi; Tao Ren; Anna Bruchez; Kyungae Lee; Claire Marie Filone; Lisa Hensley; Qi Li; Daniel Ory; Kartik Chandran; James Cunningham;

  • 作者单位

    Division of Hematology, Department of Medicine, Brigham and Women's Hospital, Boston, Massachusetts 02115, USA;

    Division of Hematology, Department of Medicine, Brigham and Women's Hospital, Boston, Massachusetts 02115, USA Division of Infectious Disease, Department of Medicine, Children's Hospital, Boston, Massachusetts 02115, USA;

    New England Regional Center of Excellence for Biodefense and Emerging Infectious Diseases, Harvard Medical School, Boston, Massachusetts 02115, USA;

    Division of Hematology, Department of Medicine, Brigham and Women's Hospital, Boston, Massachusetts 02115, USA;

    New England Regional Center of Excellence for Biodefense and Emerging Infectious Diseases, Harvard Medical School, Boston, Massachusetts 02115, USA;

    Division of Hematology, Department of Medicine, Brigham and Women's Hospital, Boston, Massachusetts 02115, USA United States Army Medical Research Instituteof Infectious Diseases, Virology Division, Frederick, Maryland 21702, USA;

    United States Army Medical Research Instituteof Infectious Diseases, Virology Division, Frederick, Maryland 21702, USA;

    Division of Hematology, Department of Medicine, Brigham and Women's Hospital, Boston, Massachusetts 02115, USA;

    Diabetic Cardiovascular Disease Center, Washington University School of Medicine, Saint Louis, Missouri 63110, USA;

    Division of Hematology, Department of Medicine, Brigham and Women's Hospital, Boston, Massachusetts 02115, USA;

    Division of Hematology, Department of Medicine, Brigham and Women's Hospital, Boston, Massachusetts 02115, USA Department of Microbiology and Immunology, Harvard Medical School, Boston, Massachusetts 02115, USA;

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  • 正文语种 eng
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