Open AccessIn silico analysis and experimental validation of azelastine hydrochloride (N4) targeting sodium taurocholate co‐transporting polypeptide ( NTCP ) in HBV therapy
Author(s) -
Fu L.L.,
Liu J.,
Chen Y,
Wang F.T.,
Wen X.,
Liu H.Q.,
Wang M.Y.,
Ouyang L.,
Huang J.,
Bao J.K.,
Wei Y.Q.
Publication year - 2014
Publication title -
cell proliferation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.647
H-Index - 74
eISSN - 1365-2184
pISSN - 0960-7722
DOI - 10.1111/cpr.12117
Subject(s) - in silico , in vitro , drugbank , chemistry , pharmacology , computational biology , virology , microbiology and biotechnology , biology , drug , biochemistry , gene
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 HB sAg ( IC 50 = 7.5 μ m ) and HB eAg ( IC 50 = 3.7 μ 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.