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Development of a dual screening assay for the efficient search for antiviral Hepatitis C entryinhibitors from microorganisms

开发双重筛选方法，从微生物中有效寻找抗病毒丙型肝炎进入抑制剂

基本信息

批准号：
315473972
负责人：
Dr. Birte Plitzko
金额：
--
依托单位：
Whitney Laboratory for Marine Bioscience
依托单位国家：
德国
项目类别：
Research Fellowships
财政年份：
2016
资助国家：
德国
起止时间：
2015-12-31 至 2016-12-31
项目状态：
已结题

来源：
https://gepris.dfg.de/gepris/projekt/315473972?language=en
关键词：
Development dual screening assay efficient

项目摘要

The search for more efficient antiviral substances with less side effects is a predominant topic in drug research. Currently, only few viral infectious diseases have satisfactory drug therapies. The pool of natural products continues to be an excellent source for new drug candidates and lead structures. Despite of their great potential natural products are very rarely tested for antiviral activity due to the complexity of cell-based antiviral assays and their lack of high throughput. My research project aims to develop a dual screening approach that allows to screen natural product libraries more efficiently and in a medium throughput for antiviral activity. For this purpose, the biosensor platform Octet® RED96 is used to identify small molecules with high affinities to a target protein in a newly developed protein-based binding assay. For this project I will use the Hepatitis C (HCV) envelope protein E1/E2 to find potential new entryinhibitors. Hits from this binding assay will then be evaluated for entryinhibitory activity in a cell-based assay with single round HCV infectivity assay using HCV-pseudotyped viruses. Active compounds will be fully characterized in terms of structure, activity as well as binding to the viral protein and they will serve immediately as valuable lead structures.This dual screening concept offers a substantially more efficient way to screen for natural products for drug therapy. The combination of the two in vitro assays has the potential to accelerate the drug discovery process and to find antiviral compounds and structural leads that will contribute to the development of new antiviral drugs or serve as molecular probes to study viral infections.

寻找更有效、副作用更少的抗病毒物质是药物研究中的一个主要课题。目前，只有少数病毒感染性疾病有令人满意的药物治疗。天然产物池仍然是新的候选药物和铅结构的极好来源。尽管天然产物具有巨大的潜力，但由于基于细胞的抗病毒检测的复杂性和缺乏高通量，很少对其进行抗病毒活性测试。我的研究项目旨在开发一种双重筛选方法，允许更有效地筛选天然产物库，并以中等吞吐量进行抗病毒活性筛选。为此，在新开发的基于蛋白质的结合分析中，使用生物传感器平台Octet®RED96来识别与目标蛋白质具有高亲和力的小分子。在这个项目中，我将使用丙型肝炎病毒包膜蛋白E1/E2来寻找潜在的新的进入抑制剂。然后，通过使用丙型肝炎病毒假型病毒的单轮丙型肝炎病毒感染性试验，在基于细胞的试验中评估来自该结合试验的HITS进入抑制活性。活性化合物将在结构、活性以及与病毒蛋白的结合方面得到充分表征，它们将立即成为有价值的先导结构。这种双重筛选概念为药物治疗提供了一种更有效的天然产物筛选方法。这两种体外测试的结合有可能加速药物发现过程，并找到有助于开发新的抗病毒药物或用作研究病毒感染的分子探针的抗病毒化合物和结构线索。