Hepatitis B virus large envelope protein PreS1 domain (PreS1)

The PreS1 domain is a critical N-terminal extension of the Hepatitis B virus (HBV) large envelope protein (L protein) that mediates viral attachment and entry into host hepatocytes (UniProt P03141). It serves as the essential ligand for the sodium/taurocholate cotransporting polypeptide (NTCP), a bile acid transporter that HBV and Hepatitis D virus (HDV) hijack to gain entry into the cell (Yan et al., 2012). Because HDV is a subviral pathogen that requires the HBV envelope for its assembly and transmission, the PreS1 domain is a shared vulnerability for both viruses. The N-terminal portion of PreS1 is post-translationally myristoylated, a modification that is strictly required for its high-affinity interaction with NTCP. Therapeutic targeting of this domain, most notably with the entry inhibitor bulevirtide, involves using synthetic peptides that mimic the PreS1 sequence to competitively block the NTCP receptor (Bogomolov et al., 2016). This approach prevents the infection of new hepatocytes and is currently a primary treatment strategy for chronic HDV, which often leads to rapid progression of liver cirrhosis and hepatocellular carcinoma (EMA, 2020).

Other names

HBV L protein PreS1 domainLarge surface protein PreS1LHBs PreS1Hepatitis B virus large S protein PreS1

Entry inhibition by competitive binding to the sodium/taurocholate cotransporting polypeptide (NTCP) receptor, thereby preventing viral attachment and internalization.