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

The Hepatitis B virus (HBV) Pre-S1 envelope region is a critical domain of the large surface protein (L-HBsAg) located on the outer envelope of the virus (UniProt P03141). It plays a pivotal role in the viral life cycle by mediating the specific attachment and entry of HBV and Hepatitis D virus (HDV) into human hepatocytes (PubMed: 22976217). This process occurs through the high-affinity binding of the N-terminal myristoylated Pre-S1 domain to the sodium/taurocholate cotransporting polypeptide (NTCP), which serves as the primary functional receptor (PubMed: 23152530). Because this interaction is essential for establishing infection, the Pre-S1 region has become a major therapeutic target for entry inhibitors. Drugs like bulevirtide mimic the Pre-S1 sequence to competitively inhibit NTCP binding, effectively preventing the spread of the virus to healthy cells (EMA/445405/2020). Additionally, the Pre-S1 region is a target for neutralizing antibodies and is utilized in next-generation vaccines to elicit a more robust immune response compared to standard HBsAg vaccines (PubMed: 34653434).

Other names

HBV Pre-S1 domainLarge surface proteinL-HBsAgPre-S1 regionHepatitis B virus large envelope protein

Bulevirtide, a synthetic myristoylated peptide derived from the Pre-S1 domain, binds to and inactivates the sodium/taurocholate cotransporting polypeptide (NTCP) receptor on the hepatocyte membrane, thereby blocking the entry of HBV and HDV into the cells (PubMed: 23152530). Monoclonal antibodies targeting this region neutralize the virus by preventing its attachment to the host receptor and potentially enhancing the clearance of HBsAg (PubMed: 32814515).