The in vitro hepatitis C virus infection system as a drug discovery tool

体外丙型肝炎病毒感染系统作为药物发现工具

• 批准号: 7270929
• 负责人: Amine Osman Noueiry
• 金额: $ 10.07万
• 依托单位: APATH, LLC
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-09-15 至 2008-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7270929
• 关键词: Address; Adverse effects; Alternative Therapies; Animal Model; Antiviral Agents; Attention; Attenuated; Basic Science; Cirrhosis; Communities; Complementary DNA; Condition; Cultured Cells; Data; Development; Drug Industry; Drug resistance; Epidemic; Genomics; Genotype; Goals; Health system; Hepatitis C; Hepatitis C virus; In Vitro; Infection; Infectious hepatitides; Interferon-alpha; Interferons; Licensing; Life; Liver Failure; Liver diseases; Malignant neoplasm of liver; Marketing; Methods; Mutation; Outcome; Patients; Pharmaceutical Preparations; Population; Primary carcinoma of the liver cells; Protocols documentation; Public Health; Publishing; Reagent; Replicon; Reporting; Research; Resistance; Ribavirin; Rights; Series; System; Testing; Transfer Agreement; Universities; Vaccines; Viral; Virus; Zein; anti-hepatitis C; base; drug development; drug discovery; expectation; inhibitor/antagonist; liver transplantation; mutant; physical property; small molecule; tool

DESCRIPTION (provided by applicant): Hepatitis C virus (HCV) infection is a major cause of liver disease throughout the world. Existing therapies are suboptimal and the search for alternative therapies is imperative. Recent years have seen a tremendous increase in efforts to identify more effective therapies against HCV. These efforts have been greatly facilitated by sub-genomic HCV replicon systems that efficiently replicate in cell culture. However, despite all the benefits of these replicon systems, the lack of an infectious HCV system in cell culture is still an impediment to all aspects of HCV studies, particularly the development of HCV anti-viral therapies. The recent development of an HCV clone that is infectious in cell culture (termed HCVcc) can directly address these shortcomings. The focus of this proposal is to develop the HCVcc system as a more useful tool for drug development. This includes identifying culture methods for increasing HCVcc titer, developing HCVcc genotypes relevant to the dominant drug development target, and facilitating drug cross-resistance studies by generating mutant infectious HCV viruses that harbor drug resistance mutations reported against experimental anti-HCV compounds presently being developed and evaluated. Results obtained here will not only directly benefit drug development efforts, but will also provide critical information and reagents to a rapidly-developing field of basic research. Infectious HCV for drug discovery.

描述（由申请人提供）：丙型肝炎病毒（HCV）感染是世界范围内肝脏疾病的主要原因。现有的治疗方法是次优的，寻找替代疗法势在必行。近年来，在确定更有效的丙肝病毒治疗方法方面的努力取得了巨大进展。在细胞培养中有效复制的亚基因组HCV复制子系统极大地促进了这些努力。然而，尽管这些复制子系统有很多好处，但在细胞培养中缺乏感染性HCV系统仍然是HCV研究的各个方面的障碍，特别是HCV抗病毒治疗的发展。最近开发的在细胞培养中具有传染性的HCV克隆（称为HCVcc）可以直接解决这些缺点。本提案的重点是开发HCVcc系统，使其成为更有用的药物开发工具。这包括确定提高HCVcc滴度的培养方法，开发与主要药物开发靶点相关的HCVcc基因型，以及通过产生突变的感染性HCV病毒来促进药物交叉耐药研究，这些突变含有目前正在开发和评估的实验性抗HCV化合物的耐药突变。在这里获得的结果不仅将直接有利于药物开发工作，而且还将为快速发展的基础研究领域提供关键信息和试剂。