Hope on the horizon: Emerging therapies for hepatitis D

Figure 1 Hepatitis D virus life cycle and therapeutic strategies. Hepatitis D virus (HDV) (and hepatitis B virus) entry is facilitated by the Sodium taurocholate co-transporting polypeptide (NTCP), which binds HBV surface antigen (HBsAg). Entry inhibitors, including Bulevirtide and monoclonal antibodies, can act to prevent viral entry. Replication of the HDV genome (HDV G) and the hepatitis B virus genome is nuclear, and one proposed mechanism of action of nucleic acid polymers is inhibition of this phase. HDV mRNA is used to make hepatitis D large antigen (HDAg-L). The HDAg-L is prenylated (which can be inhibited by prenylation inhibitors) and, along with HDV G, is used to assemble the HDV ribonucleoprotein (RNP). The HDV RNP is enveloped in the Golgi apparatus by HBsAg. Nucleic acid polymers can prevent the release of the HBsAg, while siRNA strategies can help reduce the amount of HBsAg made. The signaling pathways employed by interferons are given in the insets, and these mediate broader antiviral activity. (Created in BioRender (2025) https://BioRender.com/hrg3zi7). IFNα: Interferon-alpha.