Hepatitis B virus DNA polymerase (HBV Pol) (HBV Pol)

The Hepatitis B virus (HBV) DNA polymerase, also known as the P protein, is a multifunctional enzyme essential for the replication of the hepatitis B virus [1, 2]. It possesses four distinct domains: a terminal protein (TP) domain, a spacer region, a reverse transcriptase (RT) domain, and a ribonuclease H (RNase H) domain [1, 4]. The enzyme is unique among polymerases for its protein-priming activity, where it uses a tyrosine residue in its own TP domain to initiate DNA synthesis [1, 3]. It facilitates the conversion of pre-genomic RNA (pgRNA) into relaxed circular DNA (rcDNA) through RNA-directed DNA synthesis, DNA-directed DNA synthesis, and the degradation of the RNA template via its RNase H activity [2, 4]. Chronic infection with HBV, driven by continuous viral replication, is a leading cause of liver cirrhosis and hepatocellular carcinoma [4, 8]. Consequently, the HBV DNA polymerase is the primary therapeutic target for chronic hepatitis B treatment [3, 7]. Current frontline therapies consist of nucleoside and nucleotide reverse transcriptase inhibitors (NRTIs), such as entecavir and tenofovir, which act as chain terminators to halt viral DNA synthesis [3, 5]. However, long-term therapy faces challenges such as the emergence of drug-resistant mutations and the persistence of the viral reservoir in the form of covalently closed circular DNA (cccDNA) [8, 13].

Other names

P proteinHepatitis B virus reverse transcriptaseHBV polymeraseRNA-directed DNA polymeraseDNA-directed DNA polymeraseRibonuclease H

Nucleoside/Nucleotide Reverse Transcriptase Inhibitors (NRTIs) that act as chain terminators and inhibit protein priming and DNA elongation.