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

美国国家科学基金会的这一快速反应研究(RAPID)项目将支持一种计算方法，以了解埃博拉病毒蛋白质的结构，这些蛋白质对融合到细胞和引起感染至关重要。目前还没有针对埃博拉疫情的有效治疗方法。如果研究人员成功，这项提议的结果将为药物设计提供目标。一旦确定了目标蛋白的结构，就可以使用计算药物筛选方法来检查已有的化合物的大型数据库，这些化合物可以用来防止病毒对感染者的作用。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，使病毒能够进入宿主细胞。这段包膜糖蛋白形成一个环，将病毒锚定在宿主细胞膜上。本项目旨在确定该环在发夹前中间态的构象，以此为目标设计小分子和多肽抑制剂，以防止病毒与宿主细胞之间的膜融合。这项工作应该会导致与治疗和/或预防埃博拉感染相关的药物发现的新目标。

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.