PEPTIDE-BASED INHIBITORS OF ENVELOPED VIRUS ASSEMBLY

基于肽的包膜病毒组装抑制剂

• 批准号: 3547902
• 负责人: MILTON J SCHLESINGER
• 金额: $ 20.41万
• 依托单位: WASHINGTON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1991
• 资助国家: 美国
• 起止时间: 1991-09-30 至 1995-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3547902
• 关键词: Sindbis virus; Vesiculovirus; antiviral agents; cooperative study; disease /disorder model; glycoproteins; high performance liquid chromatography; influenza; mass spectrometry; membrane proteins; microorganism hemagglutinin; model design /development; peptide analog; peptide chemical synthesis; protein sequence; respiratory syncytial virus; synthetic peptide; tissue /cell culture; virion; virus envelope; virus protein; virus replication

This proposal focuses on the development of peptide-based antiviral agents that can selectively block assembly of enveloped viruses. The structures of the peptides correspond to short sequences of amino acids in the cytoplasmic domains of viral transmembranal glycoproteins that are postulated to interact with viral matrix proteins and nucleocapsids during virus assembly. Preliminary results showing that the addition of such peptides to cultured cells infected with influenza, vesicular stomatitis or Sindbis viruses inhibit release of newly synthesized viruses indicate that this approach has therapeutic potential. Inhibition was selective for the peptide specific to the individual virus and did not affect host cells under the conditions tested. We plan to extend our preliminary results with influenza virus by determining the structure of the smallest peptide that is most effective for inhibiting release of infectious virions. From these data, non- peptide compounds whose structures are based on conformational mimicry would be synthesized and tested for therapeutic potency in a variety of biological systems. In addition peptides mimicking cytoplasmic domains of glycoproteins in respiratory syncytial virus and the vaccine strain of yellow fever virus (used as a model system for human pathogenic flaviviruses) will be tested with laboratory-adapted strains growing in cultured cells.

该建议重点是基于肽的抗病毒的发展 可以选择性地阻断包膜病毒的代理。 这 肽的结构对应于氨基酸的短序列 在病毒跨膜糖蛋白的细胞质结构域中 假设与病毒基质蛋白和核蛋白质相互作用 在病毒组装期间。 初步结果表明添加 这种肽是感染了流感，水泡的培养细胞 气孔炎或印象病毒抑制了新合成的释放 病毒表明这种方法具有治疗潜力。 抑制作用是针对特定肽的选择性 病毒，在测试条件下不影响宿主细胞。 我们 计划通过流感病毒扩展我们的初步结果 确定最有效的最小肽的结构 用于抑制传染性病毒体的释放。 从这些数据，非 结构基于构象模仿的肽化合物 将在各种 生物系统。 另外，模仿细胞质结构域的肽 呼吸综合病毒和疫苗菌株中的糖蛋白 黄热病病毒（用作人类致病性的模型系统 黄病毒）将通过实验室适应的菌株进行测试 培养的细胞。