Blocking The Hepatitis C Virus Into Host Cells By The Membrane Fusion Inhibitors

Hepatitis C, which is spread through sexually, blood, mother-to-foetus is a global epidemic fectious disease. Hepatitis C virus (HCV) is a major pathogen to cause Hepatitis C. About170illion people worldwide have been infected by HCV and the trend is rising year by year. HCV fection may cause liver cirrhosis, eventually leading to liver cancer. Currently, interferon (combined ith ribavirin) is usually used to treat HCV infection. Unfortunately, the interferon treatment may lead a series of side effects including fever, anemia, liposotrichia, and depression. In this context, there is (?)urgent need to develop more effective anti-virus drugs to combat HCV infection. However, there is not been any membrane fusion inhibitor for anti-HCV purpose yet. In our proposed research, we ant to develop a fusion inhibitor to treat HCV.HCV envelope glycoprotein E2binding to the host cell receptor is a critical step of HCV into the11. Studies have found that CD81is the main receptor of HCV-E2, and CD81-LEL D helix is a key ea for interaction of HCV-E2with CD81. In this study, we use the RCM strategy to stabilize the;ptide conformation to synthesize a series of stapled peptides, which simulate D helix secondary ructure. These stapled peptides can be competitive combination with HCV-E2in order to inhibit the teraction of CD81LEL and HCV-E2, which blocking the process of HCV into host cells. Though ti-HCV infection experiments, we find that anti-HCV activity of stapled peptide has been greatly iproved.Lastly we got the stapled peptide CD81-Pep6, which has the highest activity to resist fferent genotypes of HCV. Chymotrypsin stability experiments further find that the CD81-Pep6has a (?)ong anti-enzymatic ability. This study will provides a new idea for anti-HCV drug development, and cceed in finding CD81-Pep6, which has the potential to become the first HCV fusion inhibitors.