Hepatitis B virus DNA polymerase reverse transcriptase domain (HBV polymerase RT domain)

The Hepatitis B virus DNA polymerase reverse transcriptase domain (HBV polymerase RT domain) is a multifunctional enzyme domain essential for hepatitis B virus (HBV) replication. It catalyzes the reverse transcription of the pre-genomic RNA (pgRNA) into relaxed circular DNA (rcDNA) within the viral capsid, acting as both an RNA-dependent and DNA-dependent DNA polymerase, with an integrated ribonuclease H activity for RNA template degradation. The polymerase is organized into four domains: terminal protein (TP, necessary for protein priming and encapsidation), spacer, reverse transcriptase (RT, focal drug target), and C-terminal RNase H. The RT domain is specifically targeted by all currently approved oral anti-HBV drugs except interferon, making it one of the most validated antiviral targets in virology. Effective inhibition of this domain suppresses HBV replication but does not eradicate the virus, with long-term therapy leading to risks of resistance and toxicities, highlighting the ongoing need for next-generation inhibitors and combination strategies.

Other names

Hepatitis B polymeraseHBV polymeraseHepatitis B reverse transcriptaseHBV RTP protein RT domain

Inhibition of reverse transcription (nucleos(t)ide analogs act as chain-terminators, incorporating into viral DNA); Some agents inhibit protein priming function; RNase H inhibition disrupts RNA template degradation necessary for replication