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

The Hepatitis B virus (HBV) preS domain is a vital structural component of the large surface protein (L-HBsAg) located on the viral envelope (UniProt: P03138). It is divided into two distinct regions, preS1 and preS2, which are essential for the virus's ability to infect host cells and assemble new virions (PubMed: 25108115). Specifically, the N-terminal myristoylated segment of the preS1 domain serves as the ligand for the sodium taurocholate cotransporting polypeptide (NTCP), the primary receptor for HBV and Hepatitis D virus (HDV) entry into hepatocytes (PubMed: 32735833). This interaction is a prerequisite for viral internalization and the establishment of chronic infection, which can lead to severe liver pathologies including cirrhosis and hepatocellular carcinoma (NIH: LiverTox). Because the preS domain is indispensable for viral entry, it has become a significant therapeutic target for antiviral drug development. The drug bulevirtide, a synthetic lipopeptide derived from the preS1 sequence, acts as a competitive inhibitor of NTCP, effectively blocking the entry of HBV and HDV into susceptible hepatocytes (EMA: Hepcludex Summary). This mechanism of action helps limit the spread of the virus within the liver and is particularly effective in treating chronic Hepatitis D co-infections. Beyond entry, the preS domain also plays a role in the secretion of subviral particles and the regulation of the host immune response during infection.

Other names

preS1 domainpreS2 domainLarge hepatitis B surface proteinL-HBsAgHBV L proteinHepatitis B virus envelope protein preS region

Entry inhibition by competitively blocking the interaction between the viral preS1 domain and the host sodium taurocholate cotransporting polypeptide (NTCP) receptor.