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The SARS-CoV-2 nucleocapsid (N) protein is a highly conserved, multifunctional structural protein essential for the viral life cycle [1, 2]. Its primary function is to package the positive-sense viral RNA genome into a ribonucleoprotein (RNP) complex, which then interacts with the membrane (M) protein to facilitate viral assembly [1, 5]. Beyond its structural role, the N protein is involved in viral replication and transcription, and it acts as an interferon antagonist to help the virus evade the host's innate immune response [2, 11]. Due to its high abundance and conservation across variants, the N protein is the primary target for rapid antigen diagnostic tests and is a key focus for developing broad-spectrum therapeutics, such as siRNA (e.g., ALN-COV) and small molecule inhibitors (e.g., K31) [8, 18]. However, its high immunogenicity has been linked to the induction of cytokine storms in severe COVID-19 cases, presenting a therapeutic challenge [17].
Inhibition of viral RNA packaging and assembly; RNA interference targeting the N gene transcript; Antagonism of host interferon signaling
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