HIV Rev as a Therapeutic Target

HIV Rev 作为治疗目标

• 批准号: 6589912
• 负责人: DAVID M REKOSH
• 金额: $ 22.2万
• 依托单位: UNIVERSITY OF VIRGINIA
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-09-30 至 2004-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6589912
• 关键词: AIDS therapy; antiAIDS agent; cell line; cooperative study; enzyme activity; enzyme inhibitors; enzyme linked immunosorbent assay; human immunodeficiency virus; method development; polymerase chain reaction; reverse transcriptase inhibitors; tissue /cell culture; virus RNA; virus replication

DESCRIPTION (provided by applicant): Current AIDS treatments are largely directed against the enzymatic activities of reverse transcriptase or protease. Because of the limitations of these inhibitors, there remains a great need to develop alternative therapeutics that target other essential viral activities. This application, a collaborative effort between investigators at University of Virginia and investigators at Message Pharmaceuticals, proposes to further explore HIV Rev as a therapeutic target. The experiments include further analysis of previously identified Rev inhibitors, as well as the development of a high throughput cell-based screen that will enable the identification of novel inhibitors. This screen will be utilized to probe the specialized chemical libraries of Message Pharmaceuticals comprising nearly 150,000 compounds. The compounds have been selected to have properties that would be expected to target RNA and RNA-protein interactions. Potential Rev inhibitors will be sent to the University of Virginia for further characterization and testing, where the compounds will for tested for their ability to inhibit HIV replication. Assays will also be performed to determine where the inhibitor acts in the Rev export pathway. At the end of this project we expect to have a series of compounds inhibiting various steps in the Rev pathway. These compounds should be useful as potential leads in the development of anti-HIV drugs and also as tools to further elucidate the Rev export pathway.

描述（由申请人提供）：目前的艾滋病治疗主要针对逆转录酶或蛋白酶的酶活性。由于这些抑制剂的局限性，仍然非常需要开发针对其他基本病毒活性的替代疗法。该应用是弗吉尼亚大学研究人员和 Message Pharmaceuticals 研究人员的合作成果，建议进一步探索 HIV Rev 作为治疗靶点。这些实验包括对先前鉴定的 Rev 抑制剂进行进一步分析，以及开发基于细胞的高通量筛选，从而能够鉴定新型抑制剂。该屏幕将用于探测 Message Pharmaceuticals 包含近 150,000 种化合物的专业化学库。这些化合物被选择具有预期针对 RNA 和 RNA-蛋白质相互作用的特性。潜在的 Rev 抑制剂将被送往弗吉尼亚大学进行进一步的表征和测试，并测试这些化合物抑制 HIV 复制的能力。还将进行测定以确定抑制剂在 Rev 输出途径中的作用位置。在该项目结束时，我们预计会出现一系列抑制 Rev 途径中各个步骤的化合物。这些化合物应该可以作为抗 HIV 药物开发的潜在先导化合物，也可以作为进一步阐明 Rev 输出途径的工具。