7-(Chlorodifluoromethyl)-5-(2-furanyl)-N-(2-thienylmethyl)pyrazolo[1,5-a]pyrimidine-2-carboxamide

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].

HCV

[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.