The SARS-CoV-2 genome encodes four major structural proteins: (1) Nucleocapsid (N), (2) Membrane (M), (3) Envelope (E), and the (4) Spike (S) protein. Among the four coronavirus structural proteins, the spike (S) and the nucleocapsid (N) are the main immunogens (Figure 1). Key to the pathology of SARS-CoV and SARS-CoV-2 is the binding of the spike (S) protein, specifically of the S1 receptor-binding domain (RBD, aa319–541), to human ACE2 (angiotensin converting enzyme 2) receptors (Figure 1). The RBD is subject to increased rates of mutation as compared to other S protein domains and has resulted in SARS-CoV-2 RBD mutations that increase its affinity to ACE2 by 10–20-fold compared to SARS-CoV RBD (Nature 2020, 579 (7798), 270-273).

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