Development of Inhibitors Against HCV Infection

描述（由申请人提供）：丙型肝炎病毒感染是最常见的 在美国常见的慢性血液传染病。约有 每年有36，000例新感染，其中25- 30%的感染是 症状。据估计，有390万（1.8%）美国人 感染了由HCV感染引起的慢性肝病是第十位 美国成年人死亡的主要原因， 大约占所有死亡人数的1%。到目前为止，还没有一种有效的文化。 该系统可用于评价化合物体外抗HCV的活性。到 为了克服这一困难，正在使用替代动物病毒，包括 牛病毒性腹泻病毒、黄热病病毒、登革热病毒和班兹病毒。 我们已经鉴定了一种化合物（ZX-2401），其显示出显著的抗病毒活性， 对这些替代病毒的活性。本申请的总体范围 是研究这种化合物及其衍生物作为 HCV的潜在抑制剂。这些新化合物的具体目标 包括根据拟定研究的需要合成ZX-2401或衍生物， 在HCV复制子系统和细胞毒性中进行体外抗病毒研究 测试，与IFN-α结合进行研究，并进行 作用机制研究。

DESCRIPTION (Provided by applicant): Hepatitis C viral infection is the most common chronic bloodborne infection in the United States. There are about 36,000 new infections every year, and 25-30 percent of those infections are symptomatic. It is estimated that 3.9 million (1.8 percent) Americans have been infected. Chronic liver disease, which is caused by HCV infection, is the tenth leading cause of death among adults in the United States, accounting for approximately 1 percent of all deaths. To date, there is no efficient culture system available to evaluate the activity of compounds against HCV in vitro. To overcome this difficulty, surrogate animal viruses are being used, including bovine viral diarrhea virus, yellow fever virus, dengue virus, and banzi virus. We have identified a compound (ZX-2401) that shows a significant antiviral activity against these surrogate viruses. The overall scope of this application is to investigate the feasibility of this compound and its derivatives as potential inhibitors of HCV. The specific aims for these novel compounds include synthesizing ZX-2401 or derivatives as needed for the proposed studies, performing in vitro antiviral studies in HCV replicon system and cytotoxicity testing, performing studies in combination with IFN-alpha, and performing mechanism of action studies.