化学性质：                                                                                                             

描述：                                                                                                            

Nesbuvir is a novel selective inhibitor of nonstructural protein 5B (NS5B) polymerase with IC50 value of 5 nM [1].

NS5B (nonstructural protein 5B) is a viral protein found in HCV and plays an important role in HCV RNA replicate by using the viral positive RNA strand as its template and catalyzing the polymerization of rNTP during RNA replication. As the principal catalytic enzyme for HCV replication, NS5B is a viable target for HCV-RNA replication and used as a target for HCV therapy [2] [3].

Nesbuvir is a selective NS5B polymerase inhibitor and has a different selectivity with the reported ALK inhibitor crizotinib. When tested with Huh7.5 cell line, nesbuvir showed the highest selectivity for NS5B and mutations reduced the cells susceptibility [1]. In Clone A cells derived from Huh-7 cells containing approximately 1,000 genome copies of HCV genotype 1b replicon per cell, nesbuvir treatment with the concentration of 0.1 and 1 μM for 16-day reduced about 3.6 log10 and 4.2 log10 HCV RNA levels, respectively [2].

In the chimeric mouse model, nesbuvir treatment resulted in a 2.02 +/- 0.55 log reduction in HCV titer, whereas in combination with interferon using a suboptimal dose of 30 mg/kg three times per day showed a 2.44 log reduction and were better than interferon treatment only [4].

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