RNA-directed DNA polymerase (Reverse transcriptase) (RT)

RNA-directed DNA polymerase, commonly known as reverse transcriptase (RT), is a vital enzyme used by viruses such as Human Immunodeficiency Virus (HIV) and Hepatitis B Virus (HBV) to replicate their genetic material (UniProt P03366, P03145). In HIV, the enzyme converts the viral single-stranded RNA into double-stranded DNA, which is then integrated into the host genome. In HBV, the polymerase protein uses an RNA intermediate (pregenomic RNA) to synthesize the viral DNA genome via reverse transcription (StatPearls: NRTIs). Because the catalytic domains of HIV RT and HBV polymerase share significant structural homology, several drugs are effective against both targets, making them essential for managing co-infected patients (NIH: Hepatitis B and HIV Coinfection). These therapeutic agents, primarily nucleoside and nucleotide analogs like tenofovir and lamivudine, function by mimicking natural nucleotides and causing premature termination of the DNA chain during synthesis (PubChem: Tenofovir). This target is a cornerstone of modern antiviral therapy, though its high error rate leads to mutations that can result in drug resistance, necessitating the use of combination drug regimens.

Other names

Reverse transcriptaseRNA-dependent DNA polymeraseP proteinPol proteinHBV polymeraseHIV-1 reverse transcriptaseHIV-2 reverse transcriptaseDNA polymerase (RNA-directed)

Nucleoside and nucleotide reverse transcriptase inhibitors (NRTIs/NtRTIs) act as competitive substrate analogs that are incorporated into the nascent viral DNA chain, leading to premature chain termination due to the absence of a 3'-hydroxyl group. Non-nucleoside reverse transcriptase inhibitors (NNRTIs) bind to an allosteric site on the HIV-1 enzyme, causing a conformational change that inhibits DNA polymerization (StatPearls: NRTIs; UniProt P03366).