HZ-1157 is a potent hepatitis C virus (HCV) inhibitor toward HCV NS3/4A protease with IC50 value of 1.0 μmol/L [1].

The NS3 protease of HCV is a prime target for the development of anti-HCV agents because it cleaves the viral polyprotein and liberates NS3, NS4A, NS4B, NS5A, and NS5B, allowing them to function normally in viral RNA replication, and it deactivates many host proteins involved in innate immunity to foster a favorable cellular environment for HCV replication. The NS3 protease is most active when complexed with its cofactor NS4A [1].

In vitro: Huh7.5.1 cell line stably transfected with HCV NS3/4A protease reporter was established to investigate the anti-HCV mechanism of HZ-1157 (0.001~1 μmol/L). The results showed that HZ-1157 exhibited inhibitory effect on the HCV NS3/4A protease with IC50 value of 1.0 μmol/L. HZ-1157 was further tested against an infectious HCV virus (J399EM) which can infect and replicate in Huh7.5.1 cells in vitro. The results showed that HZ-1157 effectively inhibited J399EM virus replication in Huh7.5.1 cells with IC50 value of 0.82 μmol/L [1].

Reference:

[1].  Yu Y, Jing J, Tong X, et al. Discovering novel anti-HCV compounds with inhibitory activities toward HCV NS3/4A protease[J]. Acta Pharmacologica Sinica, 2014, 35(8): 1074.

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