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（由申请人提供）：该命中率提出的提议解决了以下假设：一种旨在与HIV-1包膜尖峰糖蛋白GP120结合并插入病毒膜的代理，可以使膜上指导的力向尖峰传递，从而导致其自身的膜，从而导致其自身的膜，从而在Viral of Viral of Viral of Viarectiv and deactivectiv and deactiv。该假设是基于以下愿景：（i）成熟的HIV病毒可能在渗透压上是压力，并且（ii）病毒尖峰糖蛋白GP41的一个作用是破坏病毒膜的稳定。在这项工作中，我们将使用GP120结合和膜插入域设计，测试和优化嵌合体。该项目依赖于高度互连的模拟/实验方法。如果成功，我们的结果将构成可以开发全新的病毒剂的基础。

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.

• 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