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埃博拉病毒进入机制:从分子特征到药物发现。

Ebola Virus Entry: From Molecular Characterization to Drug Discovery.

机构信息

Department of Molecular Medicine, University of Padova, IT-35121 Padova, Italy.

出版信息

Viruses. 2019 Mar 19;11(3):274. doi: 10.3390/v11030274.

Abstract

Ebola Virus Disease (EVD) is one of the most lethal transmissible infections, characterized by a high fatality rate, and caused by a member of the family. The recent large outbreak of EVD in Western Africa (2013⁻2016) highlighted the worldwide threat represented by the disease and its impact on global public health and the economy. The development of highly needed anti-Ebola virus antivirals has been so far hampered by the shortage of tools to study their life cycle , allowing to screen for potential active compounds outside a biosafety level-4 (BSL-4) containment. Importantly, the development of surrogate models to study Ebola virus entry in a BSL-2 setting, such as viral pseudotypes and Ebola virus-like particles, tremendously boosted both our knowledge of the viral life cycle and the identification of promising antiviral compounds interfering with viral entry. In this context, the combination of such surrogate systems with large-scale small molecule compounds and haploid genetic screenings, as well as rational drug design and drug repurposing approaches will prove priceless in our quest for the development of a treatment for EVD.

摘要

埃博拉病毒病(EVD)是最致命的传染性疾病之一,其特征是死亡率高,由家族的一个成员引起。最近西非(2013-2016 年)爆发的埃博拉疫情凸显了该疾病对全球公共卫生和经济构成的威胁。到目前为止,由于缺乏研究其生命周期的工具,严重缺乏高需求的抗埃博拉病毒抗病毒药物,这使得在生物安全级别 4(BSL-4)控制之外筛选潜在的活性化合物受到阻碍。重要的是,开发了替代模型来在 BSL-2 环境中研究埃博拉病毒的进入,例如病毒假型和埃博拉病毒样颗粒,这极大地促进了我们对病毒生命周期的了解,并确定了有希望的干扰病毒进入的抗病毒化合物。在这种情况下,将这些替代系统与大规模小分子化合物和单倍体遗传筛选、合理药物设计和药物再利用方法相结合,将在我们开发埃博拉病毒病治疗方法的过程中证明是无价的。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c124/6466262/0115aa166ecd/viruses-11-00274-g001.jpg

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