• 主题
高级搜索  >
历史搜索 清空历史
首页> 美国卫生研究院文献>Cells >The Thrombopoietin Receptor Agonist Eltrombopag Inhibits Human Cytomegalovirus Replication Via Iron Chelation
【2h】

The Thrombopoietin Receptor Agonist Eltrombopag Inhibits Human Cytomegalovirus Replication Via Iron Chelation

机译：血小板生成素受体激动剂Eltrombopag通过铁螯合抑制人类巨细胞病毒复制

代理获取
本网站仅为用户提供外文OA文献查询和代理获取服务，本网站没有原文。下单后我们将采用程序或人工为您竭诚获取高质量的原文，但由于OA文献来源多样且变更频繁，仍可能出现获取不到、文献不完整或与标题不符等情况，如果获取不到我们将提供退款服务。请知悉。
页面导航
  • 摘要
  • 著录项
  • 相似文献
  • 相关主题

摘要

The thrombopoietin receptor agonist eltrombopag was successfully used against human cytomegalovirus (HCMV)-associated thrombocytopenia refractory to immunomodulatory and antiviral drugs. These effects were ascribed to the effects of eltrombopag on megakaryocytes. Here, we tested whether eltrombopag may also exert direct antiviral effects. Therapeutic eltrombopag concentrations inhibited HCMV replication in human fibroblasts and adult mesenchymal stem cells infected with six different virus strains and drug-resistant clinical isolates. Eltrombopag also synergistically increased the anti-HCMV activity of the mainstay drug ganciclovir. Time-of-addition experiments suggested that eltrombopag interfered with HCMV replication after virus entry. Eltrombopag was effective in thrombopoietin receptor-negative cells, and the addition of Fe prevented the anti-HCMV effects, indicating that it inhibits HCMV replication via iron chelation. This may be of particular interest for the treatment of cytopenias after hematopoietic stem cell transplantation, as HCMV reactivation is a major reason for transplantation failure. Since therapeutic eltrombopag concentrations are effective against drug-resistant viruses, and synergistically increase the effects of ganciclovir, eltrombopag is also a drug-repurposing candidate for the treatment of therapy-refractory HCMV disease.
机译：血小板生成素受体激动剂Eltrombopag已成功用于抵抗人类巨细胞病毒（HCMV）相关的免疫调节和抗病毒药物难治性血小板减少症。这些作用归因于Eltrombopag对巨核细胞的作用。在这里，我们测试了Eltrombopag是否也可以发挥直接的抗病毒作用。 Eltrombopag的治疗浓度抑制了人成纤维细胞和成年间充质干细胞中HCMV复制，这些成纤维细胞和成年间充质干细胞感染了六种不同的病毒株和耐药株。 Eltrombopag还协同增加了主要药物更昔洛韦的抗HCMV活性。添加时间实验表明，埃洛姆帕帕克干扰病毒进入后HCMV复制。 Eltrombopag在血小板生成素受体阴性细胞中有效，并且Fe的添加阻止了抗HCMV的作用，表明它通过铁螯合抑制了HCMV复制。这对于造血干细胞移植后的血细胞减少症的治疗可能特别感兴趣，因为HCMV重新激活是移植失败的主要原因。由于治疗性Eltrombopag浓度可有效抵抗耐药性病毒，并协同增强更昔洛韦的作用，Eltrombopag还是治疗难治性HCMV疾病的药物替代药物。

著录项

相似文献

  • 外文文献
  • 中文文献
  • 专利
代理获取

客服邮箱：kefu@zhangqiaokeyan.com

京公网安备：11010802029741号 ICP备案号：京ICP备15016152号-6 六维联合信息科技 (北京) 有限公司©版权所有

  • 客服微信

  • 服务号