Target intelligence / Profile preview

DNA polymerase, RNA-dependent RNA polymerase, and Reverse transcriptase

Molecular classification
Enzyme, Polymerase family, Retroviral enzyme, Telomerase reverse transcriptase
01

Overview

DNA polymerase, RNA-dependent RNA polymerase (RdRp), and Reverse transcriptase (RT) are three distinct classes of enzymes essential for nucleic acid synthesis and viral replication. - DNA polymerases catalyze the synthesis of DNA from a DNA template and are essential in cellular and some viral DNA replication. - RNA-dependent RNA polymerases catalyze the synthesis of RNA from an RNA template; these are critical for the replication of RNA viruses and have no direct counterpart in uninfected mammalian cells. - Reverse transcriptases catalyze the synthesis of complementary DNA from an RNA template (reverse transcription), a process exploited by retroviruses (like HIV), telomerase, and retrotransposons. These enzymes are key targets for antiviral drug development, as specific inhibitors can prevent viral genome replication. Due to their central roles in nucleic acid metabolism, mistargeting can lead to toxicity or off-target effects, particularly for drugs that can also affect human polymerases. The presence or activity of these enzymes is a defining biomarker in monitoring certain infections and in understanding the molecular basis of some cancers.

Other names
DNA-dependent DNA polymerase (DdDp)RdRpRNA replicaseRTRNA-dependent DNA polymerase
02

Mechanism of action

Inhibition of nucleic acid synthesis via incorporation of chain-terminating nucleoside/nucleotide analogs - Direct enzyme inhibition (active site, allosteric) - Prevention of genome replication or integration

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Biological functions

DNA replicationRNA replication and transcriptionReverse transcriptioncDNA synthesisViral genome replicationViral integration
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Disease associations

Infection (viral replication: HIV, hepatitis B, influenza, coronaviruses, etc.)Cancer (retrotransposon activity, telomerase in cancer)RetrotranspositionGenome stability
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Safety considerations

Off-target inhibition of host polymerases (mitochondrial or nuclear DNA polymerases)Drug resistance (mutation in viral polymerases)Toxicities related to nucleoside/nucleotide analogs (e.g., myelosuppression, lactic acidosis)
06

Interacting drugs

Acyclovir

8 more in the full profile.

07

Biomarkers

Viral load (e.g., HIV RNA, hepatitis B DNA, SARS-CoV-2 RNA as markers for RdRp and reverse transcriptase activity)cDNA levels in retrotransposon studiesActivity assays for viral resistance monitoring

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