VIRAL PROTEIN RECEPTOR INTERACTIONS

病毒蛋白受体相互作用

• 批准号: 6240454
• 负责人: DON C WILEY
• 金额: $ 1.33万
• 依托单位: HARVARD UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1996
• 资助国家: 美国
• 起止时间: 1996-09-01 至 1998-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6240454
• 关键词: CD4 molecule; Orthomyxoviridae; X ray crystallography; acidity /alkalinity; antiAIDS agent; antiviral agents; benzylamines; chemical association; chemical binding; chemical models; computer graphics /printing; computer simulation; crystallization; drug design /synthesis /production; glycoprotein structure; hemagglutinin; human immunodeficiency virus; human tissue; ligands; nuclear magnetic resonance spectroscopy; point mutation; receptor binding; sialate; virus envelope; virus infection mechanism; virus protein

We propose collaborative experiments that combine organic syntheses, X-ray crystallography, and computational chemistry, all aimed at developing an understanding of molecular structures as a basis for the development of antiviral therapies. We plan to test whether inhibiting influenza virus infection can be accomplished by blocking the binding of the virus to its cellular receptor and/or the inhibition of viral entry by blocking the virus's membrane fusion mechanism. We propose to use three-dimensional structure of the virus surface protein (HA) responsible for these activities (receptor binding and membrane fusion) and the structures of complexes of this protein with receptor analogs as a starting point for designing and testing inhibitors. We plan to develop computational methods and to determine other structures to assist the design process. We will explore increasing the affinity of ligands, matching bivalent ligands to the virus surface lattice, and interfering with necessary conformational changes by stabilizing the membrane-fusion-inactive conformation. Our goal is to develop a structural foundation for antiviral drug design.

我们提出结合有机合成、X 射线的合作实验 晶体学和计算化学，所有这些都旨在开发 理解分子结构作为开发的基础 抗病毒疗法。 我们计划测试是否抑制流感病毒 感染可以通过阻止病毒与其结合来实现 细胞受体和/或通过阻断病毒进入来抑制 病毒的膜融合机制。 我们建议利用病毒表面蛋白的三维结构 (HA) 负责这些活动（受体结合和膜 融合）以及该蛋白质与受体的复合物的结构 类似物作为设计和测试抑制剂的起点。 我们计划 开发计算方法并确定其他结构 协助设计过程。 我们将探索增强亲和力 配体，将二价配体与病毒表面晶格相匹配，以及 通过稳定来干扰必要的构象变化 膜融合非活性构象。 我们的目标是开发一个结构性的 抗病毒药物设计的基础。