The role of SARS-CoV-2 N protein in diagnosis and vaccination in the context of emerging variants: present status and prospects

Abstract

Despite many countries rapidly revising their strategies to prevent contagions, the number of people infected with Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) continues to surge. The emergent variants that can evade the immune response significantly affect the effectiveness of mainstream vaccines and diagnostic products based on the original spike protein. Therefore, it is essential to focus on the highly conserved nature of the nucleocapsid protein as a potential target in the field of vaccines and diagnostics. In this regard, our review initially discusses the structure, function, and mechanism of action of N protein. Based on this discussion, we summarize the relevant research on the in-depth development and application of diagnostic methods and vaccines based on N protein, such as serology and nucleic acid detection. Such valuable information can aid in designing more efficient diagnostic and vaccine tools that could help end the SARS-CoV-2 pandemic.

Comprehensive genomic analysis of the SARS-CoV-2 Omicron variant BA.2.76 in Jining City, China, 2022

“…Given that viruses utilize the host’s translational machinery for protein synthesis, the A28271T mutation, which changes − 3 A to -3T in the N gene’s translation initiation region, could impair the translation efficiency of the N gene, potentially leading to diminished N protein levels in host cells [ 15 – 18 ]. The N protein, crucial for SARS-CoV-2 structure, significantly influences cytokine storm induction through the promotion of inflammatory factor production, exacerbating pneumonia in those infected [ 19 – 22 ]. Thus, a reduction in N protein expression might attenuate the inflammatory response, potentially moderating the severity of pneumonia.…”

Single intranasal immunization with a high dose of influenza vector protects against infection with heterologous influenza virus and SARS-CoV-2 in ferrets and hamsters

“…Immunofluorescence analysis confirmed the intensive accumulation of the coronavirus N antigen in the cytoplasm of infected cells. The N protein is of increased interest among coronavirus proteins capable of inducing cross-reactive response because it is one of the most abundant proteins produced during viral replication and it shares a high degree of homology among coronaviruses [42].…”

Whole Blood as a Sample Matrix in Homogeneous Time-Resolved Assay—Förster Resonance Energy Transfer-Based Antibody Detection

“…Following the roll-out of vaccines that induce an immune response against SARS-CoV-2 S [19], the detection of S-specific antibodies has become less relevant or obsolete in serological COVID-19 diagnoses. However, as the majority of vaccines do not induce an immune response against the SARS-CoV-2 N [20], the detection of N-specific antibodies has become a useful tool for retrospectively demonstrating exposure to SARS-CoV-2 in the vaccinated population [21,22]. The evidence suggests that the titers against SARS-CoV-2 S following vaccination or COVID-19 have a relatively short half-life when judged by the presence of neutralizing antibodies [23][24][25].…”