Interaction of immunosuppressants with HCV antivirals daclatasvir and asunaprevir: combined effects with mycophenolic acid

Figure 1 Hepatitis C virus replication is effectively inhibited by daclatasvir and asunaprevir. Huh7-ETluc cells were cultured with increasing concentrations of DCV (A) or ASV (B). The luciferase activity in these cells is a direct measure of HCV replication. HCV replication was significantly inhibited by 0.01 and 0.1 nmol/L DCV and 1 and 10 nmol/L ASV (mean of 13 independent experiments performed in triplicate, P < 0.001 Mann-Whitney test); The luciferase signal in Huh7-PGK-luc cells, stably expressing luciferase, was not affected by any concentration of DCV (C) or ASV (D), indicating that the observed effect in HUh7-ETluc is not due to non-specific inhibition of luciferase (mean of 7 experiments performed in triplicate); HCV replication in the infectious JFH model was effectively inhibited by DCV (E) at all tested concentrations (mean of 4-6 independent experiments measured in duplicate, P = 0.004 for 0.01 nmol/L DCV, P = 0.11 for 0.05 nmol/L DCV and P = 0.007 for 0.1 nmol/L DCV), as well as by 5 nmol/L and 10 nmol/L ASV (F) (mean of 4-6 independent experiments measured in duplicate, P = 0.01 for 5 nmol/L ASV and P = 0.007 for 10 nmol/L ASV). HCV: Hepatitis C virus; DCV: Daclatasvir; ASV: Asunaprevir; MPA: Mycophenolic acid; DAAs: Direct acting antivirals.