Hepatitis B virus surface antigen PreS domain (HBsAg PreS)

The PreS domain of the Hepatitis B virus surface antigen (HBsAg) is a critical structural component of the viral envelope, comprising the PreS1 and PreS2 regions found on the Large (L) and Middle (M) surface proteins. The PreS1 region is particularly significant as it contains the essential binding site for the sodium taurocholate cotransporting polypeptide (NTCP), the primary receptor for HBV entry into human hepatocytes [1][2]. By mediating viral attachment and internalization, the PreS domain is indispensable for the establishment and maintenance of HBV and Hepatitis D virus (HDV) infections [3]. Therapeutically, this domain is targeted by entry inhibitors like bulevirtide, which mimics the PreS1 sequence to competitively block NTCP, and by third-generation vaccines that include PreS1 and PreS2 to provide superior immunogenicity compared to traditional S-antigen vaccines [4][5]. Additionally, monoclonal antibodies targeting the PreS domain, such as GC1102, are being developed to neutralize the virus and reduce the circulating viral load in chronic patients [6]. The domain also plays a role in viral assembly and the secretion of subviral particles, making it a focal point for strategies aimed at achieving a functional cure for chronic hepatitis B [7]. Its high conservation across HBV genotypes makes it an attractive target for broad-spectrum antiviral interventions [8].

Other names

PreS1 domainPreS2 domainHBV PreS regionLarge surface protein PreS domainMiddle surface protein PreS domainHBV L-protein N-terminus

Inhibition of viral entry by blocking the PreS1-NTCP interaction; neutralization of circulating virions by monoclonal antibodies; and induction of protective anti-PreS1 and anti-PreS2 immune responses via vaccination.