Fig. 1
Experimental and mathematical system for quantifying antiviral activity of hepatitis C virus (HCV) drug(s): a Schematic representation of the method for quantifying HCV replication level. The assay uses HCV subgenomic replicons for genotype 1b and 2a carrying a fusion of the firefly luciferase gene (Luc) with or without the neomycin phosphotransferase (Neor). The replicons autonomously and persistently replicate in Huh-7.5.1 cells [18, 19]. Cells were incubated for 72 h with or without drug(s) then harvested and luciferase activity detected. Inhibition of HCV replication was quantified as the luciferase activity in drug-treated cells, relative to untreated cells. b Log–Log plots of dose-response curves normalized by IC50 (x-axis), determined from HCV genotype 1b subgenomic replicon assay of NS3 protease inhibitors (PIs; TPV, DPV, ASV, SMV), nucleoside-type NS5B polymerase inhibitor (NI; SOF), non-nucleoside-type NS5B polymerase inhibitors (NNIs; VX, DAS, NSV, TGV), NS5A inhibitors (NS5AIs; DCV, LDV), interferon (IFNα), and cyclophilin inhibitors (CIs; CsA, CSY). Each point represents the mean of three experiments. Least-square regression analysis was used to fit Eq.(1) to the corresponding dose-response curve for estimation of IC50 and m value for each drug against HCV genotype 1b. c Log–Log plots of dose-response curves from HCV genotype 2a subgenomic replicon assay of PIs (ASV, SMV), NI (SOF), NNIs (DAS), and NS5AIs (DCV, LDV). Each point represents the mean of three experiments. Least-square regression analysis was used to fit Eq. [1] to the corresponding dose-response curve for each drug against HCV genotype 2a. d Dose-response curves for hypothetical drugs with m = 1 and 5. Drugs with a higher m value show stronger antiviral activity at the same normalized drug concentration