期刊
CELL PROLIFERATION
卷 47, 期 4, 页码 326-335出版社
WILEY
DOI: 10.1111/cpr.12117
关键词
-
类别
资金
- Key Projects of the National Science and Technology Pillar Program [2012BAI30B02]
- National Natural Science Foundation of China [U1170302, 81160543, 81260628, 81303270, 81172374]
- Shenyang Science and Technology Project [F12-157-9-00]
Objectives: The aim of this study was to explore sodium taurocholate co-transporting polypeptide (NTCP) exerting its function with hepatitis B virus (HBV) and its targeted candidate compounds, in HBV therapy. Materials and methods: Identification of NTCP as a novel HBV target for screening candidate small molecules, was used by phylogenetic analysis, network construction, molecular modelling, molecular docking and molecular dynamics (MD) simulation. In vitro virological examination, q-PCR, western blotting and cytotoxicity studies were used for validating efficacy of the candidate compound. Results: We used the phylogenetic analysis of NTCP and constructed its protein-protein network. Also, we screened compounds from Drugbank and ZINC, among which five were validated for their authentication in HepG 2.2.15 cells. Then, we selected compound N4 (azelastine hydrochloride) as the most potent of them. This showed good inhibitory activity against HBsAg (IC50 = 7.5 mu M) and HBeAg (IC50 = 3.7 mu M), as well as high SI value (SI = 4.68). Further MD simulation results supported good interaction between compound N4 and NTCP. Conclusions: In silico analysis and experimental validation together demonstrated that compound N4 can target NTCP in HepG2.2.15 cells, which may shed light on exploring it as a potential anti-HBV drug.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据