Hepatitis B virus large surface protein pre-S1 domain (HBV pre-S1 (preS1))

The hepatitis B virus surface antigen comprises three envelope proteins—small (S), middle (M), and large (L)—encoded from a single open reading frame containing pre-S1, pre-S2, and S domains; the L protein uniquely contains the N-terminal pre-S1 extension that is critical for infectivity and assembly[4][7]. The pre-S1 domain mediates initial HBV attachment and receptor engagement on hepatocytes, with a conserved N-terminal myristoylated sequence and residues approximately 2–48 (including a core 9–18 segment) functioning as key receptor-binding determinants, while downstream residues 49–75 modulate this activity[5][6][7]. Structurally, pre-S1 is a natively unstructured polypeptide containing multiple “pre-structured motifs,” particularly within residues 11–50, which align with functional hepatocyte-binding regions and likely act as recognition elements for receptor interaction[1]. Pre-S1 also contributes to virion morphogenesis: its C-terminal residues interact with the HBV core particle during envelopment, in concert with an interaction site in the S domain cytosolic loop[4]. Clinically, pre-S1-derived myristoylated lipopeptides can block HBV infection in vitro and in vivo by competitively inhibiting pre-S1–mediated entry, a mechanism exploited by the entry inhibitor bulevirtide (Myrcludex B)[6][7]. Pre-S region mutations can impact viral entry, assembly, antigenicity, and serologic marker performance, with implications for disease course and diagnostics[2][3].

Other names

Hepatitis B virus pre-S1HBV preS1 domainLarge HBsAg pre-S1 domainpreS1 region of hepatitis B surface antigenLHBs pre-S1

Competitive inhibition of pre-S1–NTCP interaction at the hepatocyte surface by myristoylated pre-S1 mimetic peptides, preventing HBV/HDV entry[6][7]