Spn4A.RRLL(s)-expressing cells with compounds such as mevalonate, oleate, and cholesterol resulted in an incomplete rescue of HCV infection, suggesting that the antiviral activity of our proteinbased inhibitor cannot be explained solely by the decreased availability of lipids in these cells. This also supports our hypothesis that reduced LDLR levels may compromise HCV entry into Spn4A.RRLL(s)-treated hepatocytes. LDLR, a well-established SREBP-regulated gene, has been repeatedly shown to support HCV entry into hepatocytes [69, 80] . Also, no significant reductions in HCV RNA levels were observed in Spn4A. RRLL(s)-treated cells harbouring subgenomic HCV replicons or following full-length genomic HCV RNA transfection in Huh-7.5.1 cells. Altogether, these studies indicate that the observed decline in HCV RNA levels following HCV infection may result from compromised HCV entry.