Hepatitis B virus large surface protein PreS1 domain (HBV PreS1)

The Hepatitis B virus (HBV) PreS1 antigen is a critical domain located at the N-terminus of the Large (L) surface protein (L-HBsAg) of the HBV envelope [1.1.2]. It plays a fundamental role in the viral life cycle by mediating the high-affinity binding of the virus to its primary receptor on human hepatocytes, the sodium taurocholate cotransporting polypeptide (NTCP) [1.2.1]. This interaction is the essential first step for viral entry and the establishment of infection [1.2.5]. Beyond entry, the PreS1 domain is involved in virion assembly and export, and it contains potent T-cell and B-cell epitopes, making it a significant target for both therapeutic and prophylactic interventions [1.2.2, 1.5.2]. Drugs targeting this antigen, such as the monoclonal antibody libevitug (HH-003), aim to neutralize the virus and block its attachment to liver cells [1.3.1, 1.3.4]. Clinically, serum levels of PreS1 antigen and the PreS1/HBsAg ratio serve as important biomarkers for monitoring viral replication, liver fibrosis progression, and the risk of developing hepatocellular carcinoma [1.4.1, 1.5.1]. The development of inhibitors for this target represents a major shift toward entry-blocking strategies in the management of chronic hepatitis B and D [1.3.2].

Other names

HBV PreS1/S1 antigenPreS1 regionLarge envelope proteinL-HBsAgLarge surface proteinS1 antigenHepatitis B virus PreS1 antigen

Neutralization of the virus by binding to the PreS1 domain, which blocks the interaction between the viral envelope and the host sodium taurocholate cotransporting polypeptide (NTCP) receptor, thereby preventing viral attachment and entry into hepatocytes [1.2.1, 1.3.1].