RT Journal Article SR Electronic(1) A1 Kota, S. A1 Coito, C. A1 Mousseau, G. A1 Lavergne, J.-P. A1 Strosberg, A. D.YR 2009 T1 Peptide inhibitors of hepatitis C virus core oligomerization and virus production JF Journal of General Virology, VO 90 IS 6 SP 1319 OP 1328 DO https://doi.org/10.1099/vir.0.008565-0 PB Microbiology Society, SN 1465-2099, AB Hepatitis C virus (HCV) nucleocapsid assembly requires dimerization of the core protein, an essential step in the formation of the virus particle. We developed a novel quantitative assay for monitoring this protein–protein interaction, with the goal of identifying inhibitors of core dimerization that might block HCV production in infected Huh-7.5 hepatoma cells. Two core-derived, 18-residue peptides were found that inhibited the dimerization of a fragment of core comprising residues 1–106 (core106) by 68 and 63 %, respectively. A third, related 15-residue peptide displayed 50 % inhibition, with an IC50 of 21.9 μM. This peptide was shown, by fluorescence polarization, to bind directly to core106 with a K d of 1.9 μM and was displaced by the unlabelled peptide with an IC50 of 18.7 μM. When measured by surface plasmon resonance, the same peptide bound core169 with a K d of 7.2 μM. When added to HCV-infected cells, each of the three peptides blocked release, but not replication, of infectious virus. When measured by real-time RT-PCR, the RNA levels were reduced by 7-fold. The 15-residue peptide had no effect on HIV propagation. Such inhibitors may constitute useful tools to investigate the role of core dimerization in the virus cycle., UL https://www.microbiologyresearch.org/content/journal/jgv/10.1099/vir.0.008565-0