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

The Hepatitis B virus (HBV) polymerase is a multi-functional enzyme essential for the replication of the HBV genome. It possesses four primary domains: the terminal protein (TP) involved in priming, a spacer region, the reverse transcriptase (RT) domain responsible for DNA synthesis, and the RNase H domain which degrades the pregenomic RNA template (UniProt P03156). The RT domain contains the active site, characterized by highly conserved motifs such as the YMDD (tyrosine-methionine-aspartate-aspartate) sequence, which coordinates the catalytic metal ions required for nucleotide incorporation (PMID: 22434296). In the viral life cycle, this enzyme converts pregenomic RNA into partially double-stranded relaxed circular DNA (rcDNA) through a complex process of protein-primed reverse transcription. Because of its central role in viral persistence and its distinctiveness from human polymerases, the HBV RT active site is the primary target for current first-line antiviral therapies, including entecavir and tenofovir. Chronic inhibition of this enzyme significantly reduces viral load, thereby slowing the progression of liver cirrhosis and reducing the risk of hepatocellular carcinoma (PMID: 29939116; NIH/LiverTox).

Other names

HBV PolP proteinHepatitis B virus reverse transcriptaseHepatitis B virus DNA polymeraseRNA-directed DNA polymeraseDNA-directed DNA polymerase

Nucleoside/nucleotide reverse transcriptase inhibitors (NRTIs) act as chain terminators; they are phosphorylated into active triphosphates, compete with natural dNTPs for binding to the active site of the HBV polymerase, and once incorporated into the nascent DNA strand, prevent further elongation due to the lack of a 3'-hydroxyl group (PMID: 22434296; PMID: 29939116).