Background:

Anguizole is a selective inhibitor of NS4B with IC50 value of 310 nM [1].

NS4B (nonstructural protein 4B) is a viral protein which was found in hepatitis C virus and was a key regulator in HCV replication complex formation. It is reported that NS4B plays a pivotal role in HCV replication via inducing a specific membrane rearrangement and designating membranous web. NS4B-AH2, comprising amino acid 42 to 66, is identified as a major regulator for NS4B oligomerization [2].

Anguizole is a potent NS4B inhibitor and targets the second amphipathic helix of NS4B (NS4B-AH2). When tested with HCV virus, anguizole treatment significantly disrupted NS4B-AH2-mediated biological functions of NS4B which played an important role in HCV life cycle [3]. In Huh7.5 cells transferring a plasmid expressing NS4B fused in frame with GFP, 5μM anguizole treatment (48 hours) altered the distribution of NS4B MAF pattern which inhibited HCV life cycle [1].

参考文献:
[1].? Bryson, P.D., et al., A small molecule inhibits HCV replication and alters NS4B's subcellular distribution. Antiviral Res, 2010. 87(1): p. 1-8.
[2].? Gouttenoire, J., et al., Aminoterminal amphipathic alpha-helix AH1 of hepatitis C virus nonstructural protein 4B possesses a dual role in RNA replication and virus production. PLoS Pathog, 2014. 10(10): p. e1004501.
[3].? Choi, M., et al., A hepatitis C virus NS4B inhibitor suppresses viral genome replication by disrupting NS4B's dimerization/multimerization as well as its interaction with NS5A. Virus Genes, 2013. 47(3): p. 395-407.