%0 Journal Article
%T Up-regulation of glycolipid transfer protein by bicyclol causes spontaneous restriction of hepatitis C virus replication
%A Hu Li
%A Jianrui Li
%A Jinhua Chen
%A Junjun Cheng
%A Lihua Wang
%A Limin Zhao
%A Meng-Hao Huang
%A Pei Lan
%A Qiang Li
%A Rong Xue
%A Wenjing Li
%A Xiaoqin Lv
%A Yongfeng Yang
%A Zhouyi Wu
%A Zonggen Peng
%J Archive of "Acta Pharmaceutica Sinica. B".
%D 2019
%R 10.1016/j.apsb.2019.01.013
%X Bicyclol is a synthetic drug for hepatoprotection in clinic since 2004. Preliminary clinical observations suggest that bicyclol might be active against hepatitis C virus (HCV) with unknown mechanism. Here, we showed that bicyclol significantly inhibited HCV replication in vitro and in hepatitis C patients. Using bicyclol as a probe, we identified glycolipid transfer protein (GLTP) to be a novel restrictive factor for HCV replication. The GLTP preferentially bound host vesicle-associated membrane protein-associated protein-A (VAP-A) in competition with the HCV NS5A, causing an interruption of the complex formation between VAP-A and HCV NS5A. As the formation of VAP-A/NS5A complex is essential for viral RNA replication, up-regulation of GLTP by bicyclol reduced the level of VAP-A/NS5A complex and thus inhibited HCV replication. Bicyclol also exhibited an inhibition on HCV variants resistant to direct-acting antiviral agents (DAAs) with an efficacy identical to that on wild type HCV. In combination with bicyclol, DAAs inhibited HCV replication in a synergistic fashion. GLTP appears to be a newly discovered host restrictive factor for HCV replication, Up-regulation of GLTP causes spontaneous restriction of HCV replication
%K Bicyclol
%K Hepatitis C virus
%K Glycolipid transfer protein
%K Host restrictive factor
%K Protein interaction
%U https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6663943/