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