High-throughput screening of virus-and host-targeted suppressors of HCV infection

点击翻译按钮获取中文摘要

In the present study period, we have conducted high-throughput and comprehensive screening of drugs, physiologically active compounds and small synthetic compounds that suppress HCV replication by using HCV infection and replication cell culture.(1) By using HCV Feo replicon, we conducted cell-based screening of 8, 000 diversity-oriented synthesis(DOS) compounds. We initially selected 41 compounds that suppress HCV replication and further validation identified 5 epoxide compounds that had low IC50.(2) We screened 4, 000 synthetic compounds and identified 5 compounds that suppress HCV replicon and HCV-JFH1 cell culture. We further conducted structure-activity relation(SAR) analyses and identified essential molecular structure for the antiviral activity.(3) We screened serine-rich(SR) protein kinases and identified 4 anti-HCV compounds. By integrating above results, we will further give better understanding of HCV infection life cycle and molecular targets of antiviral activity.