Structure of a Corona virus

SARS-CoV-2 Antigens

The enveloped RNA Virus SARS-CoV-2 consists of 4 structural proteins and 16 non-structural proteins. The 4 structural proteins are spike (S), envelope (E), nucleocapsid (N) and membrane (M).

The N protein is associated with the RNA genome, the S, E and M proteins together form the virus envelope. The S protein is a glycoprotein consisting of two domains, the S1 domain, which contains the receptor binding domain (RBD), and the S2 domain including transmembrane and endodomain. On the virus surface, the S protein forms trimeric structures, with the RBD responsible for the virus being able to attach to and fuse with the ACE2 receptor of the host cell [1].

N and S protein are major immunogenic proteins of the virus family Coronaviridae and are very well suited for serological detection of anti-SARS-CoV-2 antibodies. Recombinant versions of both proteins are already widely used in different test systems [2, 3, 4, 5].

 

Neutralizing antibodies during host immune responses are predominantly directed against the S protein, which is supposedly suitable for very specific test settings as it is less conserved within the family of Coronaviridae than the other immunogenic antigens [2, 6].
However, recent studies have shown that antibodies against the N protein are detectable earlier in mild infections than antibodies directed against the S protein [3, 7]. As an acute marker in particular, it can be beneficial to use the N protein for the detection of IgA and IgM antibodies in order to enable early sensitive detection [7]. In the further course of the immune response, the N protein antibody level decreases, whereas antibodies against the S protein are detectable for a longer time.

Four new recombinant SARS-CoV-2 antigens complement the growing SERION Immunologics raw material portfolio for the development of high quality IVD test systems. Learn more here

Membrane Protein

Component of the viral envelope that plays a central role in virus morphogenesis and assembly via its interactions with other viral proteins.

RNA

Single-stranded and non-segmented viral genome present in the virus particle.

Nucleocapsid protein

Multifunctional protein that associates with viral RNA and packages the viral genome into a helical ribonucleocapsid (RNP). It also plays a fundamental role in the assembly of the virus.

Envelope protein

Small membrane protein involved in several aspects of the virus’ life cycle, such as assembly, budding, envelope formation, and pathogenesis.

Spike protein

Contains the receptor binding domain which uses the virus to attach to and fuse with the ACE2 receptor of the host cell leading to cell entry.

Figure 1: 
Schematic illustration of a coronavirus with the RNA genome in the nucleus, the RNA associated nucleocapsid protein (N) and the structural surface proteins envelope (E), membrane (M) and spike (S).

 

References
[1] Walls et al, „Structure, Function, and Antigenicity of the SARSCoV-2 Spike Glycoprotein“ Cell 180, 281–292 April 16, 2020 ª 2020 Elsevier Inc.
[2] Meyer et. al., “Serological Assays for Emerging Coronaviruses: Challenges and Pitfalls”, Virus Research 194 (December 2014)
[3] Nisreen M.A. Okba et al., “SARS-CoV-2 Specific Antibody Responses in COVID-19 Patients“, preprint (Infectious Diseases (except HIV/AIDS), March 20th 2020)
[4] Liu W. et al., “Evaluation of Nucleocapsid and Spike Protein-Based ELISAs for Detecting Antibodies against SARS-CoV-2“, Journal of Clinical Microbiology, 30. März 2020, JCM.00461-20, jcm;JCM.00461-20v1
[5] Lassauniere et al 2020
[6] Suresh et. al Molecular Targets for Diagnostics and Therapeutics of Severe Acute Respiratory Syndrome (SARS-CoV)“, J Pharm Pharm Sci. Author manuscript; available in PMC 2009 May 7.
[7] Guo L. et al., “Profiling Early Humoral Response to Diagnose Novel Coronavirus Disease (COVID-19)“, Clinical Infectious Diseases, March 21st 2020