RNA TARGETS FOR ANTIRETROVIRAL THERAPY

这个子项目是许多利用 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可在其他CRISP条目中表示。所列机构为 中心，但不一定是研究者所在的机构。 尽管高效抗逆转录病毒疗法（HAART）取得了成功，但由于新的HIV-1遗传变异的迅速出现，帮助病毒逃避宿主免疫和多药疗法，人们仍然非常关注。因此，开发新的抗HIV治疗药物和寻找新靶点的需求仍然非常高。为此，我们已经解决了一个高分辨率的NMR结构的RNA茎环结构，SL 1，从5 '非翻译区的HIV-1 RNA基因组。这种结构具有强烈的相关基序，即富含G的内环（GRIL），并且它参与RNA基因组的二聚化和RNA包装，这是HIV-1生命周期的两个关键阶段。我们计划使用SL 1 NMR结构来进行小分子的计算筛选，寻找会干扰HIV-1生命周期的配体。

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.