SARS-CoV-2 Nucleocapsid Products

The SARS-CoV-2 Nucleocapsid protein is one of the four major structural proteins of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), the causative agent of COVID-19 (1,2). The nucleocapsid protein is an RNA-binding protein that is essential for viral assembly into a ribonucleoprotein complex and also functions in viral budding (2,3). More specifically, after viral replication and RNA synthesis, the viral genomes that are encapsulated by the nucleocapsid protein will bud into the membrane and help with mature virus formation (2). The nucleocapsid protein is synthesized as 419 amino acids (aa) in length with a theoretical molecular weight of 45.6 kDa (4). Structurally, the nucleocapsid protein contains an RNA-binding domain (N1b), a dimerization domain (N2b), and a few shorter regions (N1a, N2a, and spacer B/N3) (3). It is the N1b domain that is suggested to be involved in RNA binding (3). The nucleocapsid N1b domain contains a beta-hairpin, a loop region, and a beta-sheet core, giving it a right-handed shape (3). Conversely, the N2b domain functions in dimerization which promotes assembly into a helical filament where the dimer interface is made of two beta-strands and an alpha-helix portion (3). Inhibition of nucleocapsid assembly may be a potential target for treating COVID-19 infection.

Following SARS-CoV-2 infection, B cells and T cells display an immune response against nucleocapsid protein and nucleocapsid-specific neutralizing antibodies are produced (5). Interestingly, a study of patients who have recovered from COVID-19 revealed that there were no neutralizing antibodies against nucleocapsid protein present; however, a high presence against neutralizing spike RBD antibodies were detected (5).

References

1. Pillay T. S. (2020). Gene of the month: the 2019-nCoV/SARS-CoV-2 novel coronavirus spike protein. Journal of Clinical Pathology. https://doi.org/10.1136/jclinpath-2020-206658

2. Malik Y. A. (2020). Properties of Coronavirus and SARS-CoV-2. The Malaysian Journal of Pathology.

3. Zhu, G., Zhu, C., Zhu, Y., & Sun, F. (2020). Minireview of progress in the structural study of SARS-CoV-2 proteins. Current Research in Microbial Sciences. https://doi.org/10.1016/j.crmicr.2020.06.003

4. Uniprot (P0DTC9)

5. Shah, V. K., Firmal, P., Alam, A., Ganguly, D., & Chattopadhyay, S. (2020). Overview of Immune Response During SARS-CoV-2 Infection: Lessons From the Past. Frontiers in Immunology. https://doi.org/10.3389/fimmu.2020.01949