receptor-binding domain of the S1 subunit of severe acute respiratory syndrome coronavirus 2 Spike (S) protein
This group contains the receptor-binding domain of the S1 subunit of the spike (S) protein from highly pathogenic human virus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), also known as 2019 novel coronavirus (2019-nCoV). The CoV S protein is an envelope glycoprotein that plays the most important role in viral attachment, fusion, and entry into host cells, and serves as a major target for the development of neutralizing antibodies, inhibitors of viral entry, and vaccines. It is synthesized as a precursor protein that is cleaved into an N-terminal S1 subunit (~700 amino acids) and a C-terminal S2 subunit (~600 amino acids) that mediates attachment and membrane fusion, respectively. Three S1/S2 heterodimers assemble to form a trimer spike protruding from the viral envelope. The S1 subunit contains a receptor-binding domain (RBD), while the S2 subunit contains a hydrophobic fusion peptide and two heptad repeat regions. S1 contains two structurally independent domains, the N-terminal domain (NTD) and the C-terminal domain (C-domain). Depending on the virus, either the NTD or the C-domain can serve as the receptor-binding domain (RBD). While RBD of mouse hepatitis virus (MHV) is located at the NTD, most of other CoVs, including SARS-CoV-2 use the C-domain to bind their receptors. Recent studies found that the receptor-binding domain (RBD) of SARS-CoV-2 S protein binds strongly to human and bat angiotensin-converting enzyme 2 (ACE2) receptors. Moreover, SARS-CoV-2 RBD exhibited significantly higher binding affinity to the ACE2 receptor than SARS-CoV RBD. Due to the key role of the S protein RBD in viral attachment, it is the major target for antibody-mediated neutralization. This model corresponds to the S1 subunit C-domain that serves as the RBD for SARS-CoV-2 and most CoVs.