Hepatitis B virus large surface antigen pre-S1 domain (HBV pre-S1 or L-HBsAg (pre-S1 region))

The hepatitis B virus pre-S1 surface antigen is a 108–119 amino acid domain of the large hepatitis B surface antigen (L-HBsAg) that serves as the critical viral determinant for hepatocyte binding and entry[1][3]. Although largely unstructured, the pre-S1 contains multiple pre-structured motifs, particularly within its N-terminal 50 residues, that function as "recognition antennae" for interaction with hepatocyte-specific receptors[1][3]. The myristoylated N-terminal region, especially residues 2–48, provides the primary receptor-binding function, while residues 49–75 act as an allosteric effector to stabilize or predispose optimal receptor engagement[3]. The pre-S1 is an essential viral infectivity determinant—only 3–4 copies per virion are required for productive infection[3]. Synthetic lipopeptides derived from the pre-S1 sequence have been developed as entry inhibitors, blocking HBV infection by occupying or inactivating cellular receptors, representing a potential therapeutic strategy for hepatitis B treatment[2]. The specific sequence elements and conformational properties of pre-S1 make it an attractive target for vaccine development and antiviral drug design.

Other names

PreS1 surface antigenLarge envelope protein pre-S1 regionL-HBsAg pre-S1 domainPre-S1 infectivity determinant

Receptor blockade: Pre-S1-derived lipopeptides inhibit HBV infection by blocking or rendering nonfunctional the hepatocyte-specific receptor that mediates viral attachment. Competitive inhibition: The N-terminal pre-S1 sequence, when presented as synthetic peptides, competes with virions for receptor binding sites on hepatocytes. Sequence-specific and acylation-dependent inhibition: The lipid moiety (myristate or stearate) and specific amino acid sequences are both necessary for inhibitory activity.