Chimeric Virucides Based on a Novel Theory of Viral Metastability

基于病毒亚稳定性新理论的嵌合杀病毒剂

• 批准号: 8312616
• 负责人: CAMERON F ABRAMS
• 金额: $ 33.84万
• 依托单位: DREXEL UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-09-01 至 2014-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8312616
• 关键词: Acquired Immunodeficiency Syndrome; Address; Binding; Cells; Chimera organism; Computer Simulation; Core Protein; Cytolysis; Development; Glycoproteins; HIV; HIV Envelope Protein gp120; HIV-1; Life Cycle Stages; Lipid Bilayers; Membrane; Modeling; Polysaccharides; Property; Role; Specificity; Stress; Structure; Testing; Tropism; Viral; Viral Matrix Proteins; Virion; Virus; Vision; Work; base; design; microbicide; novel; particle; prevent; research study; simulation; theories; virucide; weapons

DESCRIPTION (provided by applicant): This HIT-IT proposal addresses the hypothesis that an agent designed to bind to HIV-1 envelope spike glycoprotein gp120 and insert into the viral membrane simultaneously can deliver a membrane-directed force to the spike, thereby causing it to porate its own membrane, resulting in outflow of viral contents and deactivation of the virus. This hypothesis is based on the vision that (i) the mature HIV virion is likely osmotically stressed, and (ii) one role of the viral spike glycoprotein gp41 is to destabilize the viral membrane. In this work, we will design, test and optimize chimerae with gp120-binding and membrane-insertion domains. The project relies on a highly interconnected simulation/experimentation approach. If successful, our results will form the basis upon which a completely new class of virucidal agents can be developed.

描述（由申请方提供）：该HIT-IT提案阐述了一种假设，即设计用于与HIV-1包膜刺突糖蛋白gp 120结合并同时插入病毒膜的试剂可以向刺突传递膜导向力，从而使刺突穿孔其自身的膜，导致病毒内容物流出并灭活病毒。这一假设基于以下观点：（i）成熟的HIV病毒粒子可能受到应激，（ii）病毒刺突糖蛋白gp 41的一个作用是使病毒膜不稳定。在这项工作中，我们将设计，测试和优化嵌合体与gp 120结合和膜插入结构域。该项目依赖于高度互连的模拟/实验方法。如果成功的话，我们的研究结果将为开发一种全新的杀病毒剂奠定基础。

项目成果

Characterization of the water defect at the HIV-1 gp41 membrane spanning domain in bilayers with and without cholesterol using molecular simulations.

使用分子模拟的胆固醇和不含胆固醇的双层中的HIV-1 GP41膜膜膜膜膜的表征。

• DOI: 10.1016/j.bbamem.2014.01.009
• 发表时间: 2014-05
• 期刊: Biochimica et biophysica acta
• 作者: Baker MK;Gangupomu VK;Abrams CF
• 通讯作者: Abrams CF