TRANSLATION INHIBITORS OF HEPATITIS C VIRUS

本研究的长期目标是开发有效对抗丙型肝炎病毒（HCV）的新型抗病毒药物。人类丙型肝炎病毒感染导致肝脏的进行性破坏，导致肝硬化和肝细胞癌的风险增加。抗病毒药物（如干扰素）在控制丙型肝炎引起的肝脏疾病方面取得了有限的成功。已经发现了两种新的分子，它们都能阻断HCV蛋白的合成，而不会对宿主细胞产生不利影响。本提案将研究这些分子单独或联合到实验动物肝脏的直接和脂质体介导的递送。此外，还将确定这些分子在小鼠肝脏和其他各种器官中的分布、稳定性和清除情况。如果成功，这些分子阻断丙型肝炎病毒感染的功效可以在黑猩猩身上进行研究。希望本文提出的实验将导致开发新的抗病毒药物有效地对抗人类丙型肝炎病毒感染。本文提出的实验将产生重要的信息，从而开发出有效对抗人类丙型肝炎病毒感染的新药。

The long term objective of this proposal is to develop novel antiviral drugs effective against hepatitis C virus (HCV). HCV infection in humans leads to progressive destruction of the liver resulting in cirrhosis and heightened risk of hepatocellular carcinoma. Antiviral drugs (such as interferon) have had limited success in controlling HCV-induced liver disease. Two novel molecules have been discovered both of which block HCV protein synthesis without adversely affecting the host cell. This proposal will examine direct and liposome-mediated delivery of these molecules individually and in combination to the liver of experimental animals. In addition, distribution, stability and clearance of these molecules in liver and various other organs of mice will be determined. If successful, the efficacy of these molecules in blocking HCV infection can be studied in chimpanzees. It is hoped that the experiments proposed here will lead to development of novel antiviral drugs effective against HCV infection in humans. PROPOSED COMMERCIAL APPLICATION The experiments proposed here should yield important information leading to development of novel drugs effective against HCV infection in humans.