Severe acute respiratory syndrome coronavirus (SARS-CoV) is a respiratory zoonotic virus first identified in February 2003 during an outbreak that emerged in China and spread to 4 other countries. The novel SARS-CoV-2 is a genetically closely related coronavirus responsible for the 2020 COVID-19 pandemic. The virus was first identified in the respiratory tract of patients with pneumonia in Wuhan, Hubei China, in December 2019 and declared a pandemic by the World Health Organization (WHO) on March 11, 2020.
SARS-CoV-2 Spike S1 (His-Tag) SARS-CoV-2 Spike Protein, S1 Subunit (His-Tag), Recombinant His-Tag at C-Terminus Molecular Weight: Calculated ~ 76 kDa. Based on 12% reducing SDS-PAGE, the apparent MW is ~85 kDa (due to the glycosylation).
SARS-CoV-2 is an enveloped RNA virus that has four main structural proteins including spike (S) glycoprotein, small envelope (E) glycoprotein, membrane (M) glycoprotein, and the nucleocapsid (N) protein. The spike or S glycoprotein is a transmembrane protein that forms homotrimers which protrude from the viral surface and facilitate the binding of envelope viruses to host cells via ACE2-receptors. The nucleocapsid (N protein) is the structural component of the virus necessary for viral RNA transcription and replication. The membrane or M protein plays a role in determining the shape of the virus envelope, helps to stabilize nucleocapsids and promotes the completion of viral assembly. The envelope or E protein is the smallest protein in the SARS-CoV-2 structure, and it plays a role in the production and maturation of this virus.
The pathogenesis of SARS-CoV-2 infection in humans manifests itself as mild symptoms to severe respiratory failure. Elderly patients and those with serious pre-existing diseases (e.g. hypertension, diabetes, obesity, and cardiovascular disease) tend to have more severe outcomes and the highest death rate. The main cause of death is from respiratory failure due to acute respiratory distress syndrome (ARDS) brought on by a rapid and uncontrolled inflammatory signaling cascade called a “cytokine storm”. The initial trigger for the cytokine storm is not yet known but it likely involves the immune system’s detection of a large quantity of viral antigens released by dying cells.
Diagnosis
Viral tests for COVID-19 that diagnose an acute infection rely on the detection SARS-CoV-2 nucleic acid or antigen using nasopharyngeal swabs. Most antigen detection assays use antibodies that recognize SARS-CoV-2 nucleocapsid protein as it is the most abundant viral protein. Spike protein has also been targeted, especially in assays that use alternative sample types such as saliva or nasal swabs that can be collected by an individual.
Serology tests to determine an individual’s immune status to SARS-CoV-2 use recombinant antigens to detect IgA, IgG or IgM specific antibodies. Tests that detect IgG/IgM to the nucleoprotein are relatively the most sensitive due to the high concentration of nucleoprotein and consequently, antibodies generated against the nucleoprotein. However, the RBD domain of the S-protein is the host attachment protein, and antibodies to RBD are more specific and can be neutralizing. (Sethuraman, N. et al (2020). Interpreting Diagnostic Tests for SARS-CoV-2.AMA. 323(22):2249-2251). To broaden an assay’s coverage and increase its sensitivity and specificity, several diagnostics manufactures use several antigens (e.g. N, S1, RBD) within a single assay.
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