Indicator cells for antiviral screening for filoviruses

描述（由申请人提供）：丝状病毒包括一些最臭名昭著的人类病原体，由于严重的出血热综合征而导致显著的发病率和死亡率。不幸的是，很少有治疗药物可用于治疗这些病毒感染。本申请的目标是使用在I期开发的基于细胞的检测来筛选对丝状病毒（如埃博拉病毒和马尔堡病毒）具有抗病毒活性的化合物。在确定许多致病性负链RNA病毒（包括丝状病毒）复制过程中涉及的顺式作用元件和顺式作用因子方面取得了重大进展。我们已经开发了一种不受感染的病毒小基因组表达系统，其中一种易于测量的酶的表达依赖于病毒复制所必需的RNA复制和转录因子。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文库已经从商业来源获得，使用新的方法来制造不同的化合物。我们将确定那些具有最有希望的化学和生物学特征的化合物，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.