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The Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) nucleocapsid (N) gene RNA is a critical component of the viral genome that encodes the multifunctional nucleocapsid protein. This RNA serves as both a genomic template for replication and a subgenomic messenger RNA (mRNA) for the translation of the N protein, which is essential for packaging the viral RNA into ribonucleoprotein complexes and facilitating viral assembly [2, 8]. In the context of COVID-19, the N gene RNA is a primary target for diagnostic testing via RT-qPCR and is increasingly recognized as a potent therapeutic target [4, 17]. Therapeutic strategies such as antisense oligonucleotides (ASOs) and small interfering RNAs (siRNAs) are designed to bind specifically to the N gene RNA, leading to its degradation or the inhibition of its translation, thereby suppressing viral replication [4, 19]. Additionally, novel small molecules are being developed to target the secondary structures of this RNA to disrupt its function [10]. Monitoring the levels of N gene RNA in patient samples serves as a key biomarker for assessing viral load and the efficacy of antiviral treatments [14, 16]. The N gene is highly conserved across variants, making its RNA an attractive target for broad-spectrum antiviral development [4, 13]. However, challenges such as efficient delivery to the lungs and potential off-target effects remain significant hurdles in the clinical application of RNA-targeted therapies [4, 19].
RNA interference (siRNA), RNase H-mediated degradation (ASO), and steric hindrance of viral replication and translation.
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