Mitochondrial complex III inhibitors specifically inhibit HEV replication. A–F) Analysis of HEV-related Gaussia luciferase activity in an Huh7.5-p6 luciferase model treated with the indicated concentrations of different complex inhibitors for 24 h (A) and 48 h (B) and in a U87-p6 luciferase model treated with indicated concentrations of different complex inhibitors for 24 h (C) and 48 h (D). real-time qPCR analysis of HEV viral RNA level in Huh7.5 (E) and U87 (F) cell-based p6 infectious models treated with indicated concentrations of different complex inhibitors for 48 h. G) Western-blot analysis of HEV ORF-2 expression in Huh7.5-p6 infectious model after treatment with indicated concentrations of different complex inhibitors for 48 h (Ctr, nontreatment control; 0.1 μM ROT, 100 μM TTFA, 0.1 μM AMA, 0.1 μM MYXO, and 1000 μM KCN). H) Real-time qPCR analysis of HEV viral RNA level in Huh7.5 cell–based p6 luciferase model treated with the indicated concentrations of ribavirin. I) Analysis of HEV-related Gaussia luciferase activity in an Hep3B-p6 luciferase model treated with the indicated concentrations of complex III inhibitors for 24 h. J) Analysis of genotype 1 HEV (Sar55/S17/luc) viral replication-related Gaussia luciferase activity in Huh7.5-Sar/S17/luc model treated with the indicated concentrations of complex III inhibitors for 48 h. The data are means ± sd of 4 independent experiments normalized to GAPDH. *P < 0.05, **P < 0.01, ***P < 0.001 vs. DMSO CTR (set as 1).