Hepatitis B virus surface protein (HBsAg) (HBsAg)

The Hepatitis B virus surface protein (HBsAg) is a critical structural component of the HBV envelope, composed of three related proteins: small (S), medium (M), and large (L). The L-protein contains the PreS1 domain, which is essential for viral entry as it binds to the sodium taurocholate cotransporting polypeptide (NTCP) receptor on human hepatocytes (UniProt: P03141, PMID: 31513964). Beyond its role in the viral life cycle, HBsAg is secreted in massive excess as non-infectious subviral particles that function as immunological decoys, exhausting the host's T-cell and B-cell responses to facilitate chronic infection (PMID: 32693109). In clinical hepatology, HBsAg is the hallmark diagnostic marker for HBV infection, and its persistent loss, known as functional cure, is the primary goal of modern therapeutic development. Current and emerging therapies target HBsAg through various modalities, including entry inhibitors like Bulevirtide, monoclonal antibodies for neutralization, and RNA interference (RNAi) or antisense oligonucleotides (ASOs) designed to silence the production of all HBsAg isoforms (PMID: 34161314). Reducing the HBsAg burden is considered a prerequisite for restoring the patient's innate and adaptive immunity against the virus.

Other names

Hepatitis B surface antigenHBV envelope proteinLarge envelope protein (L-HBsAg)Medium envelope protein (M-HBsAg)Small envelope protein (S-HBsAg)Australia antigenPre-S1/Pre-S2/S protein

Drugs targeting the Hepatitis B virus surface protein work by neutralizing circulating virions to prevent the infection of healthy hepatocytes, blocking viral entry by interfering with the PreS1-NTCP interaction, or inhibiting the synthesis and secretion of HBsAg to reduce the viral decoy load and restore the host's exhausted immune response (PMID: 32693109, PMID: 31513964).