Medical Value of SARS-CoV-2 Spike Protein

Get high medical value with Access SARS-CoV-2 IgG assay as it detects antibodies against the virus spike protein that may be more likely to confer immunity.
Medical Value of SARS-CoV-2 Spike Protein

There is an increased demand for serology testing for SARS-CoV-2 to identify people who have been exposed to the virus and who may have developed an immune response. However, there are questions about which viral protein to use as an antigen for serology testing. Some diagnostic developers are not able to be definitive because this is a new virus, although based on the information we have, the viral protein is perceived as the obvious candidate.1

The Coronavirus

Illustration of coronavirus with four structural proteins

A coronavirus contains four structural proteins, including spike (S), envelope (E), membrane (M), and nucleocapsid (N) proteins.  

The coronavirus gets its name from the spike like protrusions that look like a crown. These viruses use the spike protein to bind to proteins on the host cell to gain entry. In the case of SARS-CoV-2, the spike proteins bind angiotensin-converting enzyme 2 (ACE2 receptor) on human cells with high affinity.2

The Value of the Spike Protein

Though the coronavirus uses many different proteins to replicate and invade cells, the spike protein is the major surface protein that it uses to bind to a receptor. After the spike protein binds to the human cell receptor, the viral membrane fuses with the human cell membrane, allowing the genome of the virus to enter human cells and begin infection.3

Studies have also shown that the S protein plays the most important roles in viral attachment, fusion and entry, and it serves as a target for development of antibodies, entry inhibitors and vaccines.4–10

The coronavirus spike protein mediates entry into host cells by attaching to a receptor on respiratory cells called angiotensin-converting enzyme 2, or ACE2,11 the existence of antibodies against it may suggest neutralization of SARS-CoV-2 infection.

To assess this, a study performed a pseudovirus particle-based neutralization assay and found that there was a significantly positive correlation in the neutralizing antibody titers between pseudovirus and SARS-CoV-2. The study demonstrates that most recently discharged patients had strong humoral immunity to SARS-CoV-2.12

Research also shows that the S protein undergoes dramatic conformational changes to expose the RBD and key residues for receptor binding to enter the host cell. Given the critical role of the RBD in initiating invasion of SARS-CoV-2 into host cells, it becomes a vulnerable target for neutralizing antibodies.13

The [SARS-CoV-2] S protein plays the most important roles in viral attachment, fusion and entry, and it serves as a target for development of antibodies, entry inhibitors and vaccines.14
Tai, W., He, L., Zhang, X. et al.
Cell Mol Immunol (2020)

Access SARS-CoV-2 IgG Assay

To identify an immune response against the SARS-CoV-2 coronavirus, it is important to target the right antibodies.

The Access SARS-CoV-2 IgG assay is designed to detect antibodies to the RBD (receptor-binding domain) of the spike protein, which may be important for immunity. We know this based on:

  • Preliminary research that has been published and pre-published from across the globe
  • Discussions with reputable subject matter experts who have recommended to target the spike protein, unlike some other manufacturers who are targeting the nucleocapsid of the virus
  • Historical information about other SARS viruses

We believe that with the Access SARS-CoV-2 assay, clinicians get high medical value as it detects antibodies against the SARS-CoV-2 spike protein that may be more likely to confer immunity.

Learn more about the Access SARS-CoV-2 IgG assay.

1Petherick, A. Developing antibody tests for SARS-CoV-2. April 04, 2020. Lancet. DOI: https://doi.org/10.1016/S0140-6736(20)30788-1
2Howes L. Structure of novel coronavirus spike protein solved in just weeks. Chemical & Engineering News. February 19, 2020. Vol. 98, Issue 8. https://cen.acs.org/analytical-chemistry/structural-biology/Structure-novel-coronavirus-spike-protein/98/i8. [Accessed: May 1, 2020]
3Saplakoglu Y. Coronavirus ‘spike’ protein just mapped, leading way to vaccine. LiveScience.com. https://www.livescience.com/coronavirus-spike-protein-structure.html. February 19, 2020. [Accessed May 1, 2020]
4Du, L., He, Y., Zhou, Y., Liu, S., Zheng, B. J. & Jiang, S. The spike protein of SARS-CoV-a target for vaccine and therapeutic development. Nat. Rev. Microbiol. 7, 226–236 (2009).
5Du, L., Yang, Y., Zhou, Y., Lu, L., Li, F. & Jiang, S. MERS-CoV spike protein: a key target for antivirals. Expert Opin. Ther. Targets 21, 131–143 (2017).
6Lu, L. et al. Structure-based discovery of Middle East respiratory syndrome coronavirus fusion inhibitor. Nat. Commun. 5, 3067 (2014).
7Du, L. et al. Introduction of neutralizing immunogenicity index to the rational design of MERS coronavirus subunit vaccines. Nat. Commun. 7, 13473 (2016).
8He, Y., Li, J., Heck, S., Lustigman, S. & Jiang, S. Antigenic and immunogenic characterization of recombinant baculovirus-expressed severe acute respiratory syndrome coronavirus spike protein: implication for vaccine design. J. Virol. 80, 5757–5767 (2006).
9Liu, S. et al. Interaction between heptad repeat 1 and 2 regions in spike protein of SARS-associated coronavirus: implications for virus fusogenic mechanism and identification of fusion inhibitors. Lancet 363, 938–947 (2004).
10Wang, Q., Wong, G., Lu, G., Yan, J. & Gao, G. F. MERS-CoV spike protein: targets for vaccines and therapeutics. Antivir. Res. 133, 165–177 (2016).
11Pappas S. Scientists figure out how new coronavirus breaks into human cells. Live Science. March 11, 2020. https://www.livescience.com/how-coronavirus-infects-cells.html. [Accessed: May 1, 2020]
12Nie, J., Li, Q., Wu, J., Zhao, C., Hao, H., Liu, H., Zhang, L., Nie, L., Qin, H., Wang, M., Lu, Q., Li, X., Sun, Q., Liu, J., Fan, C., Huang, W., Xu, M., & Wang, Y. (2020). Establishment and validation of a pseudovirus neutralization assay for SARS-CoV-2. Emerging microbes & infections, 9(1), 680–686. https://doi.org/10.1080/22221751.2020.1743767
13Chen, X., Li, R., Pan, Z. et al. Human monoclonal antibodies block the binding of SARS-CoV-2 spike protein to angiotensin converting enzyme 2 receptor. Cell Mol Immunol (2020). https://doi.org/10.1038/s41423-020-0426-7
14Tai, W., He, L., Zhang, X. et al. Characterization of the receptor-binding domain (RBD) of 2019 novel coronavirus: implication for development of RBD protein as a viral attachment inhibitor and vaccine. Cell Mol Immunol (2020). https://doi.org/10.1038/s41423-020-0400-4

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Kathleen Orland
Kathleen Orland
Kathleen Orland currently serves as senior vice president and general manager for Beckman Coulter’s Clinical Chemistry Immunoassay (CCIA) business unit, leading product strategy and new product development programs across eight global sites.

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