Hepatitis B virus surface antigen (S protein) (HBsAg)

The Hepatitis B virus surface antigen (HBsAg) S protein, also known as the small envelope protein, is the primary structural component of the HBV envelope and is essential for viral assembly and infectivity (UniProt P03141). It is encoded by the S gene and plays a pivotal role in the viral life cycle by mediating attachment to host hepatocytes via interaction with the sodium taurocholate cotransporting polypeptide (NTCP) receptor (PMID: 23135315). In patients with chronic hepatitis B (CHB), the virus secretes an enormous excess of HBsAg in the form of non-infectious subviral particles, which are thought to function as an immunological decoy that suppresses the host's innate and adaptive immune responses (PMID: 32693304). Consequently, HBsAg is a major target for both preventative vaccines and novel therapeutic interventions aimed at achieving a functional cure, characterized by the permanent loss of detectable HBsAg in the serum (PMID: 34133874). Modern drug development focuses on reducing HBsAg levels through RNA interference (siRNA), antisense oligonucleotides (ASOs), and entry inhibitors, as well as neutralizing the protein using monoclonal antibodies to restore the patient's immune control over the virus (PMID: 33581040).

Other names

Small envelope proteinS-HBsAgHBV S proteinHepatitis B surface antigenHepatitis B virus major surface antigen

Drugs targeting the HBV S protein work through several mechanisms: preventative vaccines induce neutralizing antibodies (anti-HBs); monoclonal antibodies neutralize circulating virions and subviral particles; antisense oligonucleotides (ASOs) and small interfering RNAs (siRNAs) trigger the degradation of viral mRNA to inhibit protein synthesis; and nucleic acid polymers (NAPs) block the release of HBsAg from hepatocytes (PMID: 33581040, PMID: 34133874).