Recombinant SARS-CoV-2, Nucleocapsid (N) Protein

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of coronavirus disease 2019 (COVID-19), is an enveloped, single-stranded, positive-sense RNA virus that belongs to the Coronaviridae family1. The SARS-CoV-2 genome, which shares 79.6% identity with SARS-CoV, encodes four essential structural proteins: the spike (S), envelope (E), membrane (M), and nucleocapsid protein (N)2. The N protein is 46 kDa and consists of two highly conserved structural domains, the N-terminal domain (NTD) and C-terminal domain (CTD), connected by a linker region. The NTD and CTD are involved in RNA binding and self-oligomerization, respectively3,4. The primary function of the N protein is to bind to and package the viral RNA genome into a helical ribonucleoprotein complex5. The N protein is also involved in other critical steps of the viral life cycle, including transcription, replication, and modulating infected cell signaling pathways6,7. The N protein is abundantly expressed during infection and is highly conserved, sharing 90% amino acid homology with the SARS-CoV N protein (8). It is also immunogenic, and antibodies8,9 and memory T cells 10,11 targeting the N protein are present in the sera of convalescent COVID-19 patients, identifying the N protein as a suitable candidate for vaccine development and diagnostic assays. Diagnostic assays based on the N protein effectively detect antibodies in the sera of patients infected with SARS-CoV-212. The N protein also contributes to immune evasion by antagonizing antiviral RNAi13, suggesting its potential value as a targeted therapeutic.