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

NRC publication: Ye

Peroxisome proliferator-activated receptor \u3b1 antagonism inhibits hepatitis C virus replication

Hepatitis C virus (HCV) is a global health problem and a leading cause of liver disease. Here, we demonstrate that the replication of HCV replicon RNA in Huh-7 cells is inhibited by a peroxisome proliferator-activated receptor (PPAR) antagonist, 2-chloro-5-nitro-N-(pyridyl)benzamide (BA). Downregulation of PPAR[gamma] with RNA interference approaches had no effect on HCV replication in Huh-7 cells, whereas PPAR[alpha] downregulation inhibited HCV replication. Fluorescence and coherent anti-Stokes Raman scattering (CARS) microscopy demonstrate a clear buildup of lipids upon treatment with BA. These observations are consistent with the misregulation of lipid metabolism, phospholipid secretion, cholesterol catabolism, and triglyceride clearance events associated with the inhibition of PPAR[alpha]. The inhibition of HCV replication by BA may result from disrupting lipidation of host proteins associated with the HCV replication complex or, more generally, by disrupting the membranous web where HCV replicates.NRC publication: Ye