Hepatitis B virus RNA-directed DNA polymerase (HBV Pol)

The Hepatitis B virus (HBV) RNA-directed DNA polymerase is a complex, multifunctional protein essential for the replication of the HBV genome (UniProt: P03313). It is composed of four functional domains: the Terminal Protein involved in priming, a non-conserved spacer, the Reverse Transcriptase (RT) domain, and the RNase H domain (NCBI PMC: PMC4289389). During the viral life cycle, the enzyme encapsulates with pregenomic RNA (pgRNA) and catalyzes the synthesis of the viral DNA genome via reverse transcription followed by DNA-dependent DNA synthesis (StatPearls: NBK470424). This target is clinically significant as the primary site of action for nucleos(t)ide analog (NA) therapies, such as entecavir and tenofovir. These drugs act by competing with natural substrates and causing DNA chain termination, effectively suppressing viral replication and reducing liver inflammation (PubMed: 25184131). Despite its effectiveness, therapeutic challenges include the emergence of drug-resistant mutations in the RT domain and the inability of current polymerase inhibitors to eliminate the nuclear cccDNA reservoir (NCBI PMC: PMC7019141).

Other names

Hepatitis B virus P proteinHBV Reverse TranscriptaseReverse transcriptase/DNA polymeraseHBV RTP-gene product

Nucleos(t)ide analog reverse transcriptase inhibitors (NRTIs) compete with natural deoxyribonucleotide triphosphates for the active site of the HBV polymerase and cause premature DNA chain termination upon incorporation into the nascent viral DNA strand.