Hepatitis B virus surface antigen pre-S1 domain (preS1)

The hepatitis B virus surface antigen pre-S1 domain (preS1) is the N-terminal extension of the large (L) envelope protein (L-HBsAg) of hepatitis B virus. preS1 is crucial for initiating infection by mediating binding of the virus to the host hepatocyte receptor, the sodium taurocholate cotransporting polypeptide (NTCP), via a highly conserved myristoylated motif within its N-terminal region (residues 2–48). preS1 is classified as a natively unstructured protein with multiple pre-structured motifs that become functionally important during host receptor recognition and membrane fusion. This domain is the molecular target for entry inhibitors such as bulevirtide (Myrcludex B), and has been investigated for vaccine development and therapeutic antibody design. The preS1 antigen also serves as a biomarker for monitoring viral infection. Genetic variation or disruption in this region impacts HBV infectivity and morphogenesis.

Other names

preS1preS1 domainlarge (L) surface protein N-terminal domainpreS1 of L-HBsAg

Drugs like bulevirtide bind to NTCP, the host receptor, blocking the interaction between preS1 domain and NTCP and thus preventing HBV (and HDV) entry into hepatocytes Antagonist peptides or small molecules may inhibit preS1-mediated receptor binding or viral membrane fusion