Hepatitis C virus (HCV) is a 9.6-kb positive-sense, single-stranded RNA virus. The NS5B RNA-dependent RNA polymerase has enzymatic activity essential for viral replication. NM107 is a nucleoside HCV NS5B polymerase inhibitor. In HCV replicon cells (Huh-luc/neo-ET), treatment with NM107 for 48 h resulted in a concentration-dependent inhibition of HCV replication, the EC50 and CC50 were 0.48 and ＞ 100 μM, respectively. The combination of 2 μM NM107 and 0.5 μM NIM811 (a host cyclophilin inhibitor) led to a 2.1-log reduction. Furthermore, the combination of 0.5 μM NIM811 and 5 μM NM107 resulted in a 3.1-log HCV RNA reduction, which was much better than either used alone[3]. In Huh7 cultures, treatment of infected cells with 25 μM NM107 for 24 h resulted in an intracellular HCV RNA decline, consistent with NM107 blocking HCV replication. Moreover, extracellular virus titers declined in parallel with intracellular RNA levels as expected[4].
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