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RNA-directed RNA polymerase (NSP12) (NSP12)

Target
NSP12
Molecular classification
Enzyme [1], Transferase [6], RNA-directed RNA polymerase [6]
01

Overview

The SARS-CoV-2 RNA-directed RNA polymerase (NSP12) is the primary enzyme responsible for the replication and transcription of the viral genome [1, 6]. It functions as the catalytic core of the replication-transcription complex (RTC), typically requiring the co-factors NSP7 and NSP8 for optimal activity [4, 10]. By synthesizing both genomic and subgenomic RNAs, NSP12 is indispensable for the production of new viral particles and the progression of COVID-19 [6, 8]. Beyond its polymerase activity, NSP12 has been implicated in modulating the host immune response, potentially by inhibiting interferon production [2, 11]. Due to its essential role and high conservation across coronaviruses, it is a major therapeutic target [3, 13]. Drugs such as remdesivir and molnupiravir target NSP12 by acting as nucleoside analogs that cause premature chain termination or induce lethal mutations in the viral genome [1, 8].

Other names
nsp12 [1]RNA-dependent RNA polymerase [1]RdRp [1]replicase [6]non-structural protein 12 [8]Pol [1]
02

Mechanism of action

Inhibition of viral RNA synthesis through delayed chain termination (e.g., remdesivir) or the induction of lethal mutagenesis (e.g., molnupiravir) [1, 8, 14].

03

Biological functions

Viral genome replication [6]Viral transcription [6]Innate immune response suppression [2]Host translation regulation [11]RNA capping [6]
04

Disease associations

Infection [1, 4]
05

Safety considerations

Potential for off-target effects on host mitochondrial RNA polymerase [10]Emergence of drug-resistance mutations (e.g., P323L) [9]Mutagenicity concerns associated with certain nucleoside analogs like molnupiravir [1]
06

Interacting drugs

Remdesivir [1]

9 more in the full profile.

07

Biomarkers

SARS-CoV-2 viral load (RNA levels) [18]Viral replication rate [13]

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