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The hepatitis B virus (HBV) reverse transcriptase, also known as the viral polymerase or P protein, is a multifunctional enzyme essential for HBV replication. It is encoded by the largest open reading frame in the compact 3.2 kb HBV genome. This enzyme catalyzes several critical steps in the viral life cycle, including reverse transcription of pregenomic RNA (pgRNA) into relaxed circular DNA (rcDNA), and serves as a primary target for current antiviral therapies. It possesses terminal protein (TP), spacer, reverse transcriptase (RT) and RNase H domains. All currently approved oral antiviral drugs against chronic hepatitis B are nucleos(t)ide analogs that inhibit HBV RT activity. However, resistance mutations can emerge with prolonged therapy, and these drugs do not eradicate latent cccDNA reservoirs within infected hepatocytes.
Inhibition of viral DNA strand elongation by nucleos(t)ide analogs.
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