Indicator cells for antiviral screening for filoviruses

描述（由申请方提供）：丝状病毒包括一些最臭名昭著的人类病原体，并因严重出血热综合征而导致显著的发病率和死亡率。不幸的是，很少有治疗剂可用于治疗这些病毒的感染。本申请的目的是使用在I期开发的基于细胞的测定来筛选对丝状病毒（例如埃博拉病毒和马尔堡病毒）具有抗病毒活性的化合物。在鉴定包括丝状病毒在内的许多致病性负链RNA病毒复制过程中涉及的顺式作用元件和反式作用因子方面已经取得了重大进展。我们已经开发了一个infectionindependent病毒minigenome-expression系统，其中一个容易测量的酶的表达是依赖于RNA复制和转录因子，是病毒复制所必需的。该生物测定法适用于高通量筛选以鉴定抗病毒化合物。合成和天然产物化学库已经从商业来源获得，其使用新方法来制备不同的化合物。我们将确定那些具有最有希望的化学和生物学特性的化合物，以作为潜在的抗丝状病毒药物。

DESCRIPTION (provided by applicant): Filoviruses include some of the most notorious human pathogens and cause significant morbidity and mortality due to severe hemorrhagic fever syndromes. Unfortunately, very few therapeutic agents are available to treat infections with these viruses. The goal of this application is to use a cell-based assay developed in Phase I to screen for compounds with antiviral activity against filoviruses such as Ebola and Marburg viruses. Significant advances have been made in identifying the cis-acting elements and tram-acting factors involved in replication of many pathogenic negative-strand RNA viruses, including filoviruses. We have developed an infectionindependent virus minigenome-expression system in which the expression of an easily measurable enzyme is dependent on the RNA replication and transcription factors that are essential for viral replication. This bioassay is amenable to high throughput screening to identify antiviral compounds. Synthetic and natural product chemical libraries have been obtained from commercial sources that use novel approaches to make diverse compounds. We will identify those compounds with the most promising chemical and biological profiles to pursue as potential anti-filovirus drugs.