SARS-CoV-2 spike protein receptor-binding domain (non-RBM epitopes) (SARS-CoV-2 RBD (non-RBM))

The SARS-CoV-2 spike protein receptor-binding domain (RBD) is a critical component of the viral S1 subunit responsible for docking onto the host ACE2 receptor (UniProt P0DTC2). While the receptor-binding motif (RBM) within the RBD makes direct contact with ACE2, the regions outside the RBM serve as vital targets for broadly neutralizing antibodies. These non-RBM epitopes are often highly conserved across different sarbecoviruses and SARS-CoV-2 variants of concern, making them attractive for therapeutic development to combat viral evolution (Pinto et al., Nature 2020). Drugs targeting these sites, such as Sotrovimab, typically work by sterically hindering the RBD-ACE2 interaction or by preventing the conformational transitions required for membrane fusion (Cathcart et al., bioRxiv 2021). This target is central to the development of monoclonal antibody therapies and next-generation vaccines aimed at providing pan-variant protection against COVID-19 (NIH, 2023). By focusing on these conserved regions, researchers aim to create treatments that remain effective even as the virus accumulates mutations in the more plastic RBM area. Consequently, monitoring mutations in these non-RBM regions is essential for maintaining the efficacy of existing monoclonal antibody treatments.

Other names

SARS-CoV-2 RBD non-RBM regionConserved RBD epitopesCryptic RBD epitopesS1-RBD (non-RBM)SARS-CoV-2 spike protein RBD core

Neutralization of viral entry by binding to conserved epitopes outside the receptor-binding motif, leading to steric hindrance of ACE2 binding or inhibition of spike protein conformational changes required for fusion.