Hepatitis B virus large envelope protein PreS1 region (PreS1 (context: HBV L protein))

The PreS1 region is an N-terminal domain of the large envelope (L) protein of hepatitis B virus that plays a pivotal role in the viral life cycle and pathogenesis. Composed of approximately 108–119 amino acids (depending on genotype), the PreS1 region is myristoylated at its N-terminus—a modification critical for its fusion and receptor-binding activities. The myristoylated PreS1 domain is exposed on the surface of mature HBV particles, where it directly binds the sodium taurocholate cotransporting polypeptide (NTCP) receptor on hepatocytes, initiating viral entry. Additionally, hydrophobic regions within PreS1 facilitate membrane fusion, function as a fusion peptide, and mediate interactions with the viral capsid during virion maturation. These functions make PreS1 a major target for antiviral drugs and vaccine design, with small molecules and peptide mimics under development to block PreS1-mediated entry. Note: PreS1 itself is not a receptor, enzyme, or transporter, but a viral protein domain acting as a ligand for the human NTCP receptor and mediating membrane fusion, making its classification as a "therapeutic target" accurate in the context of HBV infection therapy.

Other names

PreS1 domainpre-S1 domainpre-S1 regionHBV PreS1L HBV PreS1 region

Competitive inhibition of PreS1 binding to NTCP, blocking viral entry to hepatocytes. Fusion inhibition (preventing membrane fusion and viral uptake).