Bleomycin is a potent small molecule inhibitor of hepatitis C virus replication

BIOL 94

Bojana Rakic, bojana.rakic@nrc.ca, Marc Brulotte, and John Paul Pezacki. The Steacie Institute for Molecular Sciences, National Research Council Canada/ University of Ottawa, 100 Sussex Drive, Ottawa, ON K1A 0R6, Canada
Here we demonstrate the effects of Bleomycin on Hepatitis C Virus replication. Bleomycins (BLM) are family of antitumor antibiotics, isolated from Streptomyces verticillus. BLM bind to and degrade double stranded DNA in a sequence selective manner. They have also been shown to cleave tRNA. However, in RNA, BLM-mediated cleavage occurs on the tertiary structure, not the primary sequence as is the case for DNA. Hepatitis C Virus (HCV) is a 9.6kb single stranded RNA. Its tertiary structure contains both single and double-stranded RNA. We have shown that BLM specifically target subgenomic HCV RNA without affecting the encephalomyocarditis virus (EMCV) IRES of the replicon. Our experiments show that at inhibitory concentrations, BLM affects HCV viral replication faster than cellular DNA. A possible mechanism of inhibition is that BLM target the tertiary structure of single-stranded genomic viral RNA, or dsRNA replicating intermediates, preventing HCV protein translation in the viral life cycle.