Hepatitis B virus preS1 domain (preS1)

The Hepatitis B virus preS1 domain is a region in the N-terminal part of the large (L) envelope glycoprotein of the Hepatitis B virus (HBV), typically encompassing 108–119 amino acids depending on HBV genotype[7][9]. This domain is intrinsically disordered and rich in pre-structured motifs important for its biological function[1][2]. The preS1 domain is crucial for host cell entry: its N-terminal myristoylated region specifically binds to the sodium taurocholate co-transporting polypeptide (NTCP) on hepatocytes, making it essential for HBV’s initial attachment and infection of liver cells[2][7][9]. The preS1 domain also mediates interactions with other cellular proteins (e.g., γ2-adaptin), facilitating viral assembly and export[3]. It additionally harbors a fusion peptide motif required for viral-envelope fusion with the host cell membrane[4]. Clinically, the preS1 domain is a validated antiviral target; for example, bulevirtide (Myrcludex B) is a synthetic peptide derived from preS1 that blocks NTCP, preventing HBV (and HDV) entry into hepatocytes[9]. Because targeting preS1 prevents infection at an early step, it is under active investigation for inclusion in future therapeutic and vaccine strategies[1][9].

Other names

HBV preS1preS1 surface antigenlarge (L) envelope protein preS1 domainmyristoylated preS1

Inhibition of HBV entry by blocking NTCP binding (entry inhibition); Interference with preS1-host protein interaction