RNA TARGETS FOR ANTIRETROVIRAL THERAPY

抗逆转录病毒治疗的 RNA 靶点

• 批准号: 7723522
• 负责人: THOMAS L JAMES
• 金额: $ 0.62万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-07-01 至 2009-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7723522
• 关键词: 5' Untranslated Regions; Computer Retrieval of Information on Scientific Projects Database; Dimerization; Funding; Genome; Grant; HIV-1; Highly Active Antiretroviral Therapy; Immunity; Institution; Life Cycle Stages; Ligands; Pharmaceutical Preparations; RNA; Research; Research Personnel; Resolution; Resources; Screening procedure; Source; Staging; Structure; Therapeutic; United States National Institutes of Health; Virus; antiretroviral therapy; genetic variant; small molecule; stem; success

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Despite the success of highly active antiretroviral therapy (HAART), great concern remains due to rapid emergence of new HIV-1 genetic variants that help the virus escape host immunity and multidrug therapies. Hence, the need to develop new anti-HIV therapeutic drugs and search for new targets remains very high. To this end, we have solved a high-resolution NMR structure for an RNA stem-loop structure, SL1, from the 5'-untranslated region of the HIV-1 RNA genome. This structure has strongly concerved motif, a G-rich internal loop (GRIL), and it is involved in the dimerization of the RNA genome and RNA packaging, two crucial stages of the HIV-1 life cycle. We plan to use the SL1 NMR structure to carry out a computational screening of small molecules, looking for ligands that would interfere with the HIV-1 life cycle.

该副本是利用众多研究子项目之一 由NIH/NCRR资助的中心赠款提供的资源。子弹和 调查员（PI）可能已经从其他NIH来源获得了主要资金， 因此，可以在其他清晰的条目中表示。列出的机构是 对于中心，这不一定是调查员的机构。 尽管高度活跃的抗逆转录病毒疗法（HAART）取得了成功，但由于新的HIV-1遗传变异型的快速出现，这些遗传变异症仍引起了人们的极大关注，这些变异有助于病毒逃避宿主的免疫力和多药疗法。因此，开发新的抗HIV治疗药物并寻找新靶标仍然很高。为此，我们从HIV-1 RNA基因组的5'-非翻译区域中解决了RNA茎环结构SL1的高分辨率NMR结构。该结构具有强烈的依据，是一个富含G的内环（GRIL），并且参与了RNA基因组和RNA包装的二聚化，这是HIV-1生命周期的两个关键阶段。我们计划使用SL1 NMR结构对小分子进行计算筛选，寻找会干扰HIV-1生命周期的配体。