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. 1998 Dec 1;17(23):6839–6845. doi: 10.1093/emboj/17.23.6839

Peptides that block hepatitis B virus assembly: analysis by cryomicroscopy, mutagenesis and transfection.

B Böttcher 1, N Tsuji 1, H Takahashi 1, M R Dyson 1, S Zhao 1, R A Crowther 1, K Murray 1
PMCID: PMC1171031  PMID: 9843489

Abstract

Peptides selected to bind to hepatitis B virus (HBV) core protein block interaction with the long viral surface antigen (L-HBsAg) in vitro. High resolution electron cryomicroscopy showed that one such peptide binds at the tips of the spikes of the core protein shell. The peptides contain two basic residues; changing either of two acidic residues at the spike tip to an alanine greatly reduced the binding affinity. Transfection of hepatoma cells with a replication-competent HBV plasmid gave significantly reduced production of virus in the presence of peptide, in a dose-dependent manner. These experiments show that the interaction of L-HBsAg with core particles is critical for HBV assembly, and give proof of principle for its disruption in vivo by small molecules.

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