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

Peptides selected to bind to hepatitis B virus (HBV) core protein block int eraction with the long viral surface antigen (L-HBsAg) in vitro. High resol ution electron cryomicroscopy showed that one such peptide binds at the tip s of the spikes of the core protein shell, The peptides contain two basic r esidues; changing either of two acidic residues at the spike tip to an alan ine greatly reduced the binding affinity, Transfection of hepatoma cells wi th a replication-competent HBV plasmid gave significantly reduced productio n of virus in the presence of peptide, in a dose-dependent manner. These ex periments show that the interaction of L-HBsAg with core particles is criti cal for HBV assembly, and give proof of principle for its disruption in viv o by small molecules.