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

在本研究期间，我们利用HCV感染和复制细胞培养，对抑制HCV复制的药物、生理活性化合物和小分子合成化合物进行了高通量和全面的筛选。(1)通过使用HCV Feo复制子，我们对8，000种多样性导向合成（DOS）化合物进行了基于细胞的筛选。我们最初选择了41种抑制HCV复制的化合物，并进一步验证了5种具有低IC 50的环氧化合物。(2)我们筛选了4000种合成化合物，并鉴定了5种抑制HCV复制子和HCV-JFH 1细胞培养的化合物。我们进一步进行了构效关系（SAR）分析，并确定了抗病毒活性的基本分子结构。(3)我们筛选了富含丝氨酸（SR）的蛋白激酶，并确定了4个抗HCV化合物。综合以上结果，我们将进一步加深对HCV感染生命周期和抗病毒活性分子靶点的认识。

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.