Polymerases and reverse transcriptases (RT/Pol)

Polymerases and reverse transcriptases are a broad class of enzymes responsible for the template-directed synthesis of nucleic acid polymers, playing fundamental roles in genetic replication, transcription, and repair [4, 13]. DNA polymerases synthesize DNA from DNA or RNA templates, while RNA polymerases produce RNA during transcription or viral replication [2, 9]. Reverse transcriptases are specialized RNA-dependent DNA polymerases that convert viral RNA into DNA, a process essential for the replication of retroviruses like HIV and pararetroviruses like Hepatitis B [4, 12]. These enzymes are primary therapeutic targets for a wide range of antiviral, antibacterial, and anticancer drugs [3, 6]. Pharmacological intervention typically involves nucleoside or nucleotide analogs that cause premature chain termination or non-nucleoside inhibitors that bind to allosteric sites to impede enzymatic activity [2, 18]. While highly effective, targeting these enzymes can lead to off-target effects, such as mitochondrial toxicity due to the inhibition of human mitochondrial DNA polymerase gamma [11].

Other names

NucleotidyltransferasesDNA-directed DNA polymeraseRNA-directed DNA polymeraseRNA-directed RNA polymeraseDNA-directed RNA polymeraseReverse transcriptasesRdRp

Nucleoside and nucleotide analogs act as competitive inhibitors and chain terminators; non-nucleoside inhibitors provide allosteric inhibition; and certain agents act as lethal mutagens.