Human immunodeficiency virus type 1 reverse transcriptase and Hepatitis B virus reverse transcriptase (HIV-1 RT; HBV RT)

Human immunodeficiency virus type 1 (HIV-1) reverse transcriptase and Hepatitis B virus (HBV) reverse transcriptase are essential viral enzymes that facilitate the replication of their respective viruses by converting viral RNA into DNA (UniProt P03366, P03156). HIV-1 RT is a heterodimer composed of p66 and p51 subunits, possessing both polymerase and RNase H activities, while HBV RT is a domain within the multi-functional P protein that acts as a DNA polymerase with reverse transcriptase capability (PubMed: 10657301). These enzymes are critical therapeutic targets because their inhibition effectively halts the viral life cycle and reduces viral load in patients. Several classes of drugs, most notably nucleoside and nucleotide reverse transcriptase inhibitors (NRTIs) such as tenofovir and lamivudine, are designed to target these enzymes by acting as chain terminators (PubChem: CID 464205). Because of structural similarities in the catalytic sites of these two enzymes, certain NRTIs are effective against both HIV and HBV, making them vital for managing co-infected individuals. However, the clinical utility of these inhibitors is often challenged by the emergence of site-specific resistance mutations and potential long-term safety concerns, including renal toxicity and mitochondrial dysfunction (StatPearls: NBK441923).

Other names

HIV-1 RTHBV RTHBV DNA polymeraseP proteinRNA-directed DNA polymeraseDNA-directed DNA polymeraseReverse transcriptase

Competitive inhibition of viral DNA polymerase and incorporation into the nascent DNA strand, leading to premature chain termination.