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The SARS-CoV-2 nucleocapsid protein (N protein) is a multifunctional structural protein essential for the viral life cycle, primarily responsible for packaging the viral RNA genome into a ribonucleoprotein complex (UniProt: P0DTC9). It consists of two highly conserved domains: the N-terminal domain (NTD) for RNA binding and the C-terminal domain (CTD) for dimerization, separated by a disordered central linker (PubMed: 32464098). Beyond its structural role, the N protein facilitates viral replication and transcription and acts as an interferon antagonist, helping the virus evade the host immune response (PubMed: 33053438). Because the N protein is more conserved across coronavirus variants than the Spike protein, its conserved regions are prime targets for broad-spectrum antiviral drugs and universal vaccines (PubMed: 34123231). Small molecules and peptides are being developed to disrupt its RNA-binding or dimerization capabilities, thereby halting viral assembly (PubMed: 32835028). Additionally, the N protein is the primary antigen used in rapid diagnostic tests due to its high expression levels during infection.
Inhibition of the N-terminal RNA-binding domain or the C-terminal dimerization domain to disrupt viral ribonucleoprotein complex formation and viral assembly.
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