Hepatitis B virus large surface protein (Pre-S1) (Pre-S1)

The Hepatitis B virus pre-S1 surface antigen is a key domain of the large (L) surface protein (LHBs) located on the viral envelope [1]. It plays a fundamental role in the viral life cycle by mediating the specific binding of HBV and Hepatitis D virus (HDV) to the sodium/taurocholate cotransporting polypeptide (NTCP) receptor on human hepatocytes [1, 2]. This interaction is the primary gateway for viral entry into the liver, making the pre-S1 domain a critical determinant of tissue tropism and infectivity [3]. In chronic infections, the pre-S1 antigen is often used as a marker for active viral replication and high infectivity [3]. Therapeutic strategies targeting this antigen include the entry inhibitor bulevirtide, which is a synthetic lipopeptide derived from the pre-S1 sequence that competitively blocks the NTCP receptor [2, 4]. Furthermore, the pre-S1 domain is a target for neutralizing monoclonal antibodies and is incorporated into third-generation vaccines to enhance immunogenicity and provide broader protection against HBV variants [5].

Other names

Large surface proteinL-HBsAgHBV pre-S1 domainHepatitis B virus large envelope proteinHepatitis B virus pre-S1 surface antigen

Competitive inhibition of the sodium/taurocholate cotransporting polypeptide (NTCP) receptor to prevent viral entry and neutralization of viral particles by antibodies [2, 4].