SARS-CoV-2 and SARS-CoV spike glycoprotein receptor-binding motif (RBM)

The receptor-binding motif (RBM) is a critical subdomain within the receptor-binding domain (RBD) of the spike (S) glycoprotein of SARS-CoV-2 and SARS-CoV (nih.gov). It represents the portion of the S1 subunit that directly contacts the human angiotensin-converting enzyme 2 (ACE2) receptor to facilitate viral attachment and entry into host cells (nih.gov, frontiersin.org). Spanning approximately residues 437 to 508 in SARS-CoV-2, the RBM is the primary target for the host's neutralizing antibody response and is the focus of most therapeutic monoclonal antibodies and vaccine designs (nih.gov, biorxiv.org). The RBM's structural flexibility allows it to transition between 'up' and 'down' conformations, with the 'up' state being necessary for receptor binding (nih.gov). Due to its critical role in infection, the RBM is under significant evolutionary pressure, leading to the frequent emergence of mutations that can enhance receptor affinity or enable the virus to evade existing immunity (nih.gov). Consequently, drugs targeting the RBM, such as Bamlanivimab and Sotrovimab, must be continually evaluated for efficacy against new viral variants, such as Omicron, which harbor numerous mutations in this region (nih.gov). Therapeutic intervention often involves antibodies that lock the RBD in a 'down' position or directly shield the RBM from ACE2 (nih.gov). This ongoing antigenic drift necessitates the development of broadly neutralizing antibodies that target more conserved epitopes within or adjacent to the RBM (nih.gov). Monitoring anti-RBM antibody levels serves as a key biomarker for assessing vaccine efficacy and population immunity (nih.gov).

Other names

Receptor-binding motifSpike RBMACE2-binding motifRBD motifSARS-CoV-2 S1 RBM

Neutralization of viral entry by competitively blocking the interaction between the viral receptor-binding motif (RBM) and the host angiotensin-converting enzyme 2 (ACE2) receptor (nih.gov).