RAPID: The membrane-bound structure of fusion loops of the Ebola virus envelope glycoprotein

这个国家科学基金会快速反应研究（Rapid）项目将支持一种计算方法，以了解在与细胞融合和引起感染中起重要作用的埃博拉病毒蛋白的结构。目前还没有针对埃博拉疫情的有效治疗方法。如果研究人员取得成功，这一建议的结果将为药物设计提供一个靶点。一旦确定了目标蛋白的结构，那么计算药物筛选方法就可以用来检查已经可用的化合物的大型数据库，这些数据库可以用来防止病毒对受感染个体的作用。通过这种方式，可以确定治疗病毒的新抑制剂。研究人员将使用计算方法来确定埃博拉病毒的包膜糖蛋白片段的构象，该片段插入宿主膜并促进病毒膜与宿主膜的融合，从而使病毒进入宿主细胞。包膜糖蛋白的这一部分形成一个环，将病毒固定在宿主细胞膜上。本项目旨在确定该环在发夹前中间状态的构象，为设计小分子和肽抑制剂作为阻止病毒与宿主细胞膜融合的手段提供靶点。这项工作将导致与治疗和/或预防埃博拉感染相关的药物发现的新靶点。

This NSF Rapid response Research (RAPID) project will support a computational approaches to understand the structure of Ebola virus proteins important in fusing to cells and causing infection. Currently there are no effective treatment method against Ebola outbreaks. If the investigators are successful, results of this proposal would provide a target for a drug design. Once the structure of the target protein is determined, then computational drug screening approaches can be used to examine large databases of compounds that are already available, that could be used to prevent the action of the virus on infected individuals. In this way, new inhibitors to treat the virus can be identified. The researchers will use computational approaches to identify the conformation of the segment of the envelope glycoprotein of Ebola virus that inserts into host membrane and facilitates fusion of the viral membrane with the host membrane enabling the entry of virus into the host cell. This segment of the envelope glycoprotein forms a loop to anchor the virus to host cell membrane. This project is aimed to determine the conformation of this loop in the prehairpin intermediate state, which can be target for designing small molecule and peptide inhibitors as means of preventing the membrane fusion between the virus and the host cell. The work should lead to new targets for drug discovery associated with the treatment and/or prevention of Ebola infection.