An approximate number of 250 million people worldwide are chronically infected with hepatitis B virus, making them susceptible to a
coinfection with hepatitis D virus. The
superinfection causes the most severe form of a viral
hepatitis and thus drastically worsens the course of the disease. Until recently, the only available
therapy consisted of
interferon-α, only eligible for a minority of patients. In July 2020, the EMA granted Hepcludex conditional marketing authorization throughout the European Union. This first-in-class entry inhibitor offers the promise to prevent the spread in order to gain control and eventually participate in curing
hepatitis B and D. Hepcludex is an example of how understanding the viral lifecycle can give rise to new
therapy options.
Sodium taurocholate co-transporting
polypeptide, the
virus receptor and the target of Hepcludex, and other targets of
hepatitis D therapy currently researched are reviewed in this work.
Farnesyltransferase inhibitors such as
Lonafarnib, targeting another essential molecule in the HDV life cycle, represent a promising target for
hepatitis D therapy.
Farnesyltransferase attaches a farnesyl (isoprenyl) group to
proteins carrying a C-terminal Ca1a2X (C:
cysteine, a: aliphatic
amino acid, X: C-terminal amino acid) motif like the large hepatitis D virus
antigen. This modification enables the interaction of the HBV/HDV particle and the
virus envelope proteins.
Lonafarnib, which prevents this envelopment, has been tested in clinical trials. Targeting the lifecycle of the hepatitis B virus needs to be considered in
hepatitis D therapy in order to cure a patient from both coexisting
infections.
Nucleic acid polymers target the
hepatitis B lifecycle in a manner that is not yet understood. Understanding the possible targets of the hepatitis D virus
therapy is inevitable for the improvement and development of a sufficient
therapy that HDV patients are desperately in need of.