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The Nucleocapsid phosphoprotein (N protein) is a multifunctional structural protein essential for the life cycle of coronaviruses, including SARS-CoV-2 (UniProt: P0DTC9). Its primary function is to package the viral RNA genome into a ribonucleoprotein (RNP) complex, ensuring the protection and efficient assembly of the viral particle (PubMed: 32814526). The protein consists of two conserved domains—the N-terminal RNA-binding domain and the C-terminal dimerization domain—linked by a disordered, highly phosphorylated region that regulates its activity and interaction with other viral proteins (PubMed: 32558645). In addition to its structural duties, the N protein acts as an interferon antagonist, helping the virus evade the host's innate immune system (PubMed: 33053430). Clinically, it serves as a vital biomarker for diagnostic antigen tests and serological surveys, as it is expressed at high levels during infection (PubMed: 32730415). Therapeutic strategies targeting the N protein focus on small molecules that disrupt its ability to bind RNA or dimerize, offering a potential alternative or supplement to Spike-targeted vaccines and treatments (PubMed: 33503314).
Inhibition of RNA-binding affinity, disruption of protein dimerization, and interference with the formation of the ribonucleoprotein complex to prevent viral replication and assembly.
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