Monoclonal Antibody for SARS-CoV-2 (Covid-19) Spike S1 Protein

Model of the external structure of the SARS-CoV-2 virion

Blue: envelope
Turquoise: spike glycoprotein (S)
Red: envelope proteins (E)
Green: membrane proteins (M)
Orange: glycan

Coronavirus disease 2019 (COVID-19) is a contagious disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Spike (S) glycoprotein (sometimes also called spike protein) is the largest of the four major structural proteins found on the surface of Covid-19 virion.

The function of the spike glycoprotein is to mediate viral entry into the host cell by first interacting with molecules on the exterior cell surface and then fusing the viral and cellular membranes. Spike glycoprotein is a class I fusion protein that contains two regions, known as S1 and S2, responsible for these two functions. The S1 region contains the receptor-binding domain that binds to receptors on the cell surface. Coronaviruses use a very diverse range of receptors; SARS-CoV (which causes SARS) and SARS-CoV-2 (which causes COVID-19) both interact with angiotensin-converting enzyme 2 (ACE2). The S2 region contains the fusion peptide and other fusion infrastructure necessary for membrane fusion with the host cell, a required step for infection and viral replication. Spike glycoprotein determines the virus’ host range (which organisms it can infect) and cell tropism (which cells or tissues it can infect within an organism).

The S1 region of the spike glycoprotein is responsible for interacting with receptor molecules on the surface of the host cell in the first step of viral entry. S1 contains two domains, called the N-terminal domain (NTD) and C-terminal domain (CTD). Depending on the coronavirus, either or both domains may be used as receptor-binding domains (RBD). The CTD is responsible for the interactions of SARS-CoV-2 with their receptor angiotensin-converting enzyme 2 (ACE2). The CTD of these viruses can be further divided into two subdomains, known as the core and the extended loop or receptor-binding motif (RBM), where most of the residues that directly contact the target receptor are located. Within coronavirus lineages, the S1 region is less well conserved than S2. Within the S1 region, the NTD is more conserved than the CTD.

Molecular structure of a SARS-CoV-2 spike protein trimer in the pre-fusion conformation, with a single monomer highlighted. The S1 NTD is shown in blue and the S1 CTD (which serves as the receptor-binding domain) is shown in pink. Helices show in orange and cyan form parts of S2 that will undergo conformational changes during fusion. The black bar at the bottom indicates the position of the viral membrane. From PDB: 6VSB​.

Molecular structure of a SARS-CoV-2 spike protein trimer in the pre-fusion conformation, with a single monomer highlighted.

The S1 NTD is shown in blue and the S1 CTD (which serves as the receptor-binding domain) is shown in pink. Helices show in orange and cyan form parts of S2 that will undergo conformational changes during fusion. The black bar at the bottom indicates the position of the viral membrane.

From PDB: 6VSB​.