The SARS-CoV-2 nucleocapsid (N) protein is a structural protein critical for viral replication and assembly. It binds to the viral RNA genome, forming a ribonucleoprotein complex that packages the RNA into the virion. The N protein is highly immunogenic due to its abundance during infection and conserved regions across coronaviruses, making it a primary target for antibody detection in COVID-19 diagnostics.
Following SARS-CoV-2 infection, anti-N antibodies (IgG, IgM, and IgA) are typically detectable in serum within 1–2 weeks, peaking around 3–4 weeks. These antibodies are commonly identified via immunoassays like ELISA or lateral flow assays. Unlike spike (S) protein-targeting antibodies induced by vaccines (e.g., mRNA or subunit vaccines), anti-N antibodies specifically indicate natural infection, aiding in distinguishing vaccinated individuals from those with prior COVID-19 exposure.
However, N protein mutations in emerging variants may affect antibody binding, though it remains more conserved than the spike protein. Anti-N antibodies may persist for months but wane over time, correlating with disease severity and immune memory. Their detection supports seroprevalence studies, retrospective diagnosis, and monitoring reinfections. Despite diagnostic utility, anti-N antibodies are not neutralizing, as they target structural components rather than viral entry mechanisms. Research continues to explore their role in long-term immunity and cross-reactivity with other coronaviruses.