The spike protein (S protein) is a large type I transmembrane protein ranging from 1,160 amino acids for avian infectious bronchitis virus (IBV) and up to 1,400 amino acids for feline coronavirus (FCoV) (Figure 1). In addition, this protein is highly glycosylated as it contains 21 to 35 N-glycosylation sites. Spike proteins assemble into trimers on the virion surface to form the distinctive "corona", or crown-like appearance. The ectodomain of all CoV spike proteins share the same organization in two domains: a N-terminal domain named S1 that is responsible for receptor binding and a C-terminal S2 domain responsible for fusion (Figure 2). CoV diversity is reflected in the variable spike proteins (S proteins), which have evolved into forms differing in their receptor interactions and their response to various environmental triggers of virus-cell membrane fusion.
It's been reported that 2019-nCoV can infect the human respiratory epithelial cells through interaction with the human ACE2 receptor. Indeed, the recombinant Spike protein can bind with recombinant ACE2 protein.
The coronavirus spike protein is a class I fusion protein. The formation of an α-helical coiled-coil structure is characteristic of this class of fusion protein, which contain in their C-terminal part regions predicted to have an α-helical secondary structure and to form coiled-coils. The S2 subunit is the most conserved region of the protein, whereas the S1 subunit diverges in sequence even among species of a single coronavirus (Figure 2). The S1 contains two subdomains, a N-terminal domain (NTD) and a C-terminal domain (CTD). Both are able to function as receptor binding domains (RBDs) and bind variety of proteins and sugars.
Figure 2. SARS-CoV spike protein schematic. The spike protein ectodomain consists of the S1 and S2 domains. The S1 domain contains the receptor binding domain and is responsible for recognition and binding to the host cell receptor. The S2 domain, responsible for fusion, contains the putative fusion peptide (blue) and the heptad repeat HR1 (orange) and HR2 (brown).
The roles of spike protein (S protein) in receptor binding and membrane fusion indicate that vaccines based on the spike protein could induce antibodies to block virus binding and fusion or neutralize virus infection. Among all structural proteins of SARS-CoV, spike protein is the main antigenic component that is responsible for inducing host immune responses, neutralizing antibodies and/or protective immunity against virus infection. Spike protein has therefore been selected as an important target for coronavirus vaccine and anti-viral development.
