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

The Hepatitis B virus (HBV) polymerase is a multifunctional enzyme essential for the replication of the HBV genome and serves as the primary target for antiviral therapy [1]. It is composed of four functional domains: the terminal protein involved in protein priming, a non-essential spacer, the reverse transcriptase/DNA polymerase domain, and the RNase H domain [2]. The enzyme facilitates the conversion of pregenomic RNA into relaxed circular DNA through a complex process involving reverse transcription and DNA-directed DNA synthesis [3]. Tenofovir diphosphate, the active intracellular metabolite of the prodrugs tenofovir disoproxil fumarate and tenofovir alafenamide, acts as a potent inhibitor of this enzyme [4]. By competing with the natural substrate deoxyadenosine triphosphate for incorporation into the nascent viral DNA strand, tenofovir diphosphate causes premature chain termination, thereby suppressing viral load and preventing disease progression to cirrhosis or hepatocellular carcinoma [5]. Clinical management of chronic hepatitis B relies heavily on the long-term suppression of this enzyme to reduce the risk of liver failure [3]. While highly effective, the use of nucleoside analogues can lead to the selection of drug-resistant mutations within the polymerase domain, though tenofovir has a high genetic barrier to resistance [5].

Other names

P proteinHBV reverse transcriptaseHBV DNA polymeraseHepatitis B virus P proteinHBV RT

Competitive inhibition of the viral polymerase and induction of DNA chain termination upon incorporation into the nascent viral DNA strand [4, 5].