Recombinant HCoV-NL63 N protein [His]

The Coronaviridae family consists of single-stranded positive-stranded RNA viruses that have an envelope structure and receive their name from the regularly spaced spike glycoprotein visible as a crown-like formation on the envelope surface under electron microscopy. Based on genetic characteristics and host range, the Coronaviridae family is divided into four genera.

Figure 1. Coronavirus particle
(Source: Li G, et al. 2020)

The coronavirus nucleocapsid (N) protein contains two core functional domains: The N-terminal RNA-binding domain (NTD) and C-terminal dimerization domain (CTD) connect through a serine/arginine-rich linker region (SR linker). The NTD binds RNA bases using its positively charged surface which interacts through aromatic residues and the CTD stabilizes the RNA structure by attaching to the phosphate backbone through positively charged residues to create helical nucleocapsid cores. The N protein commonly experiences phosphorylation changes at serine sites which could govern RNA binding-release behavior. SARS-CoV-2 and SARS-CoV N protein sequence identity stands at 90.52%, indicating high conservation that makes it a perfect candidate for cross-species transmission research and development of vaccines that work across multiple species.

The N protein plays a central role in the viral replication cycle: The nucleocapsid protein constructs ribonucleoprotein complexes through RNA-dependent RNA polymerase recruitment for genome replication functions while it binds the membrane protein for virion assembly control and works as a molecular chaperone for RNA folding maintenance. The functional states of N protein are regulated through phosphorylation which results in unphosphorylated forms promoting RNA packaging while phosphorylated forms boost replication activity. Due to its high expression and strong immunogenicity, the N protein serves as a core antigen for serological detection (e.g., ELISA, immunofluorescence), with cross-strain applicability in diagnostic assays. For example, SARS-CoV-2 N protein-specific monoclonal antibodies achieve high detection sensitivity (>98%). Although located within the virion, N protein-induced T-cell responses (particularly CD8⁺) are critical in infection control. Animal studies show that N protein-expressing DNA vaccines significantly reduce viral loads. Multivalent vaccines like Ad5-S+N enhance protection through the synergistic activation of neutralizing antibodies and cellular immunity to show broad-spectrum potential. Fusion protein approaches such as N-CD154 strengthen immunogenic responses through optimized antigen presentation performance.

Human coronavirus Nucleocapsid protein [His]
HCoV N protein [His]