Hepatitis D virus large envelope protein preS1 domain

The **preS1 domain of the large envelope protein** is a critical region found in the large surface glycoprotein of hepatitis B virus (HBV), which also provides the envelope for hepatitis D virus (HDV). In the context of HDV, this domain mediates specific binding to the human sodium taurocholate co-transporting polypeptide (NTCP), a liver-specific receptor that enables viral entry into hepatocytes[3][4]. The preS1 domain is myristoylated at its N-terminus, a modification essential for membrane interaction and successful infection[3]. Structural and mutational studies show that the first ~75 amino acids, particularly residues 9–15 and 2–48, are essential for binding and infectivity[3][1]. The preS1 domain not only facilitates cell attachment but also harbors the fusion peptide necessary for viral and cellular membrane fusion[1]. Drugs like **bulevirtide** (Hepcludex) exploit this interaction by mimicking preS1 and compete for NTCP binding, thus blocking HBV and HDV infection at the entry step[3]. The preS1 domain is thus a validated, clinically targeted viral determinant and a major focus for therapeutic intervention[3]. Mutation or deletion (e.g., d11) in this domain can modulate infectivity, with implications for drug resistance and vaccine design[2].

Other names

HBV/HDV preS1 domain of large envelope (L) proteinpreS1 domainHepatitis B virus preS1 region (context: in HDV, uses HBV envelope proteins)

Peptide-based entry inhibitors (e.g., bulevirtide) block preS1 domain binding to its receptor NTCP, preventing virus entry into hepatocytes[3]. Targeted mutations or deletions in preS1 (e.g., d11) modify or abolish receptor interaction, thus inhibiting infectivity[2].