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The SARS-CoV-2 RNA-dependent RNA polymerase (RdRp), primarily composed of the non-structural protein 12 (NSP12), is the central enzyme responsible for the replication and transcription of the viral RNA genome [1][2]. It operates as part of a multi-protein complex, typically requiring the accessory proteins NSP7 and NSP8 to achieve high processivity and efficiency [3]. As the engine of viral proliferation, RdRp is a critical therapeutic target for treating COVID-19, the disease caused by SARS-CoV-2 infection [4]. Antiviral agents such as remdesivir target this enzyme; remdesivir is a nucleotide analog that, once metabolized to its active triphosphate form, is incorporated into the growing RNA chain by RdRp [5]. This incorporation leads to delayed chain termination, effectively halting the synthesis of viral RNA and preventing the assembly of new virions [2][5]. Because RdRp is highly conserved among coronaviruses and lacks a human counterpart, it remains a primary focus for broad-spectrum antiviral development [1][4].
Inhibition of viral RNA synthesis through delayed chain termination following incorporation of the active nucleotide triphosphate analog into the nascent RNA strand [2][5].
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