SARS-CoV-2 is a member of the betacoronavirus genus and is closely related to SARS-CoV (Wrapp et al. 2020). In general, three structural proteins are associated with the viral envelope of coronaviruses: a membrane protein (M), an envelope protein (E) and a spike protein (S). The spike protein consists of three segments: an ectodomain (including subunits S1 and S2), a transmembrane anchor and a short intracellular tail. The trimeric transmembrane spike glycoprotein (S) mediates the coronavirus entry by receptor binding and membrane fusion. It consists of two functional subunits named S1 and S2. S1 mediates binding to the host receptor and shows a high diversity among coronaviruses. S2 induces fusion of the virus with the cellular membrane of the host and is conserved. S is synthesized as a single- chain precursor and trimerizes upon folding. Coronavirus S proteins include up to two protease cleavage sites, i.e. between the S1 and S2 subunits (S1/S2) and upstream of the fusion peptide (S2’) (Walls et al. 2017). To bind a host cell receptor, the receptor-binding domain (RBD) of S1 has do undergo hinge-like conformational movements resulting in hiding or exposing the determinants of receptor binding. There are two conformations known for the RBD: the down and the up conformation, where down leads to the receptor-inaccessible state and up leads to the receptor-accessible state, which is less stable. SARS-CoV-2 RBD consist of 223 amino acids (Lan et al. 2020). Nine cysteine residues are found within the RBD resulting in four disulfide bonds. On protein level RBD is formed by a five-stranded antiparallel beta sheet and short connecting helices. An extended insertion can be found between beta 4 and beta 7. This insertion contains the short beta 5 and beta 6 strands and is described as RBM (receptor binding motif), containing most of the residues that bind to ACE2.
To due its permanent exposure on the virus surface the S protein can be targeted in diagnostics and has potential as a vaccine candidate.