Figure 8.

HSD17B12 inhibitor INH-12 blocks HCV, ZIKV and DENV replication. (A) Chemical structure of INH-12. (B) Huh-7 cells expressing an HCV subgenomic replicon Con1b luciferase were treated with 0 to 20 µM of INH-12 for 4 days. (C) Huh7.5 cells infected with JFH-1, (D,E) with ZIKV H/PF/2013 strain and (F,G) with DENV2 16681 strain were treated with 0 to 20 µM of INH-12 for 2 days. Infectious virus titers (D,F) were measured at a MOI = 0.05 for 3 days by plaque assays. The expression of viral proteins (E,G) was determined at a MOI = 3 at 2 days post-infection by western blot. Data were normalized to control arbitrary value of 1 (D–F). Non-parametric Mann Whitney test was used to compare each condition with the control. P values ≤ 0.05 (*) are indicated in comparison with DMSO control from analysis of 3 experiments (n = 3). (H) Representative EC₅₀ and CC₅₀ curves for INH-12 on Huh7.5 cells infected with DENV-R2A and ZIKV-R2A reporter viruses two days post-infection (MOI = 0.05) and table for mean values (±SEM for n = 4).