The immune response to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is initiated by innate immune activation followed by antigen-specific T and B cell responses. An important mechanism that protects against viral diseases is the presence of virus-neutralizing antibodies, which is similar for almost all viruses that cause acute illness followed by the elimination of pathogens.
Accordingly, all currently available antiviral vaccines are primarily intended to induce virus-neutralizing antibodies. Neutralizing antibodies generally block the binding of the virus to cell receptors.
In some cases, neutralizing antibodies can prevent the conformational changes necessary for virus fusion with the cell membrane or proteolytic cleavage. Neutralizing antibodies against SARS-CoV-2 are directed against the peak protein (S), which contains multiple antigenic epitopes in the receptor-binding domain (RBD) and non-RBD epitopes.
An important neutralization mechanism is to block the binding of RBD to angiotensin-converting enzyme 2 (ACE2), the virus’s cellular receptor. RBD is located at the tip of protein S. The receptor-binding motif (RBM) consists of approximately 70 aa within RBD and represents the actual amino acids that directly interact with ACE2.
Coronaviruses get their names from the typical spikes that are formed by the spike protein (S) that inserts into the lipid bilayer membrane of the virus. The receptor-binding domain (RBD) and its receptor-binding motif (RBM) allow interaction with the cell-surface receptor ACE2 that mediates entry of the virus into host cells.
This can be blocked by neutralizing antibodies. Therefore, most of the neutralizing epitopes are found on RBD / RBM. In addition to protein S, SARS-CoV-2 has two other viral surface proteins (not shown): envelope (E) and matrix (M).