Suramin blocks hepatitis C binding to human hepatoma cells in vitro

Abstract

It was demonstrated recently that the binding of dengue virus to its target cell receptor could be effectively blocked by both heparin and by the polysulphonate pharmaceutical, Suramin [Chen et al. (1997) Nature Medicine 3:866-871]. Because both dengue and hepatitis C virus (HCV) belong to the Flaviviridae and because the HCV envelope is predicted to possess a heparin-binding motif, we tested heparin, Suramin, and a number of other polyanionic compounds for their ability to block HCV binding in vitro. The compounds, at concentrations ranging from 0.5 to 5,000 microg/ml, were tested using the human hepatoma cell line HepG2 cultured under conditions designed to enhance hepatocyte differentiation. Cells were harvested at 2 weeks postinoculation and HCV-RNA was quantified by means of a chemiluminescent reverse transcription polymerase chain reaction (PCR) assay. Suramin was found to be capable of blocking HCV binding in this system at a concentration similar to that reported to be effective against dengue virus. Removal of the viral envelope by treatment with chloroform also prevented HCV infection. Neither chondroitin sulphate nor the Suramin analogue CPD14 were able to block HCV under these conditions.