Antiviral screening against multiple viruses

描述（由申请人提供）：尽管基于细胞的筛选已经被 在整个药物发现领域成功使用，但当 筛选抗病毒化合物。这是因为它需要接种 感染性病毒到细胞上，并产生额外的感染性 子代病毒处理这种传染性物质不容易与 筛选大型化合物库的高通量过程。部分 病毒复制系统提供了一种解决这个问题的方法。病毒基因组， 缺乏一个或多个遗传元件，是执行一个 一个完整的复制周期提供了一个系统，其中病毒基因组复制 和许多其他病毒途径发生在细胞内，但没有感染性病毒， 制作。利用这些不完整的病毒基因组的筛选过程可以 鉴定涉及病毒基因组任何生物化学途径的抑制剂 复制的在本提案中，我们计划扩大这一能力， 这种方法能够同时筛查多种病毒。通过组合 细胞系，其中每一个包含一个部分复制的病毒基因组，我们可以 同时筛选针对每种病毒的抗病毒活性。在 除了测量化合物对基因组复制的影响之外， 几种病毒，该系统提供的信息的特异性， 抗病毒作用这些信息有助于评估 作用于特定的病毒靶或细胞靶， 它对病毒的间接影响。此外，该方法还允许 鉴定具有广泛抗病毒活性的化合物， 因此可以有效对抗不止一种病毒。 拟议商业应用：不可用

DESCRIPTION (Provided by applicant): Although cell-based screening has been used successfully throughout the drug-discovery field, it is problematic when screening for antiviral compounds. This is because it requires inoculation of infectious virus onto the cells and the production of additional infectious progeny virus. Handling such infectious material is not easily compatible with the high throughput process of screening large libraries of compounds. Partial viral replication systems offer a way around this problem. Viral genomes which lack one or more genetic elements that are essential for carrying out a complete replication cycle offer a system in which viral genomic replication and many other viral pathways occur within cells, but no infectious virus is produced. A screening process that utilizes these incomplete viral genomes can identify inhibitors of any biochemical pathway involved in viral genome replication. In this proposal we plan to expand the capabilities of this approach to be able to screen for multiple viruses simultaneously. By combining cell lines, each of which contain a partially replicating viral genome, we can screen for antiviral activity against each of the viruses simultaneously. In addition to measuring the effect of a compound on genomic replication of several viruses, this system provides information on the specificity of the antiviral effect. This information is helpful in accessing whether the effect is acting on a specific viral target or on a cellular target and thus exerting its effect on the virus(es) indirectly. In addition this approach allows for the identification of compounds which exhibit broad antiviral activity and could therefore be effective against more than one virus. PROPOSED COMMERCIAL APPLICATION: NOT AVAILABLE