Viral reverse transcriptase (RT) (RT)

Viral reverse transcriptase (RT) is a multifunctional enzyme essential for the replication of retroviruses, such as the Human Immunodeficiency Virus (HIV), and hepadnaviruses, such as the Hepatitis B Virus (HBV) (UniProt: P03366, P03156). It functions primarily as an RNA-directed DNA polymerase, converting the viral single-stranded RNA genome into double-stranded DNA that can be integrated into the host cell's genome or maintained as a template for viral protein synthesis (StatPearls: HIV-1 Reverse Transcriptase Inhibitors). The enzyme is multifunctional, possessing RNA-dependent DNA polymerase, DNA-dependent DNA polymerase, and RNase H activities, the latter of which degrades the RNA template during DNA synthesis (PubMed: PMC3159441). Because reverse transcription is not a standard process in human cellular replication, RT serves as a highly selective and effective target for antiviral chemotherapy (NIH: Antiviral Drug Resistance). Current therapeutic agents include nucleoside/nucleotide analogs that cause DNA chain termination and non-nucleoside inhibitors that bind allosterically to disrupt the enzyme's catalytic function (PubChem: Zidovudine). However, the clinical utility of these drugs is often challenged by the rapid emergence of viral resistance mutations and potential toxicities related to the inhibition of host mitochondrial polymerases (PubMed: 29165310).

Other names

RNA-directed DNA polymeraseReverse transcriptaseRDDPViral DNA polymeraseP protein (HBV)Reverse transcriptase/ribonuclease H

Inhibition of viral DNA synthesis through two primary mechanisms: competitive inhibition and chain termination by nucleoside/nucleotide analogs (NRTIs), and allosteric inhibition of the polymerase active site by non-nucleoside inhibitors (NNRTIs) (StatPearls: HIV-1 Reverse Transcriptase Inhibitors).