The SARS-CoV-2 spike is presented as a trimeric structure on the surface of the virus. It consists of three identical transmembrane proteins, called spike proteins, each containing two subunits: the S1 and the S2 subunit. The S1 is necessary for the recognition of the receptor on the surface of a susceptible cell. In addition, the S2 subunit is responsible for the fusion of the virus with the cell membrane of the host cell. Upon binding of the host receptor hACE2, the distal S1 domain is cleaved. This reveals the fusion machinery of the S2 subunit, which mediates the entry into the cell. Moreover, the Spike protein is heavily glycosylated by N-linked glycans that are important for the proper folding of the protein and the recognition by neutralizing antibodies. The engineered recombinant Spike protein contains specific amino acid substitutions to stabilize the prefusion conformation (2P). Furthermore, the furin cleavage site at the boundary between the S1/S2 subunits was deleted and an artificial trimerization domain was added to the C-terminal end of the monomer. Several mutants of the spike protein are known. A new SARS-CoV-2 lineage called 20H/501Y.V2, also known as lineage B.1.351 or Beta variant, exhibits several mutations. Compared to the previously circulating variants, the mutation E484K may affect neutralization by some polyclonal and monoclonal antibodies. Furthermore, the mutation N501Y may influence the binding affinity of the spike protein to hACE2. Therefore, the N501Y mutation is considered the most dangerous modification of the virus resulting in a higher transmissibility.
