SARS-CoV-2 spike protein receptor-binding motif (RBM) (SARS-CoV-2 S-RBM)

The SARS-CoV-2 spike protein receptor-binding motif (RBM) is a critical sub-region within the receptor-binding domain (RBD) of the S1 subunit of the spike glycoprotein. It represents the specific portion of the virus that makes direct contact with the human Angiotensin-Converting Enzyme 2 (ACE2) receptor to initiate cellular entry (UniProt: P0DTC2). Because the RBM is the primary interface for host cell attachment, it serves as the most significant target for neutralizing antibodies induced by vaccination or natural infection (PubMed: 32511539). Therapeutic monoclonal antibodies, such as Bamlanivimab and Sotrovimab, are designed to bind specifically to this motif to sterically hinder ACE2 interaction (PubMed: 33359671). However, the RBM is highly susceptible to mutations, leading to the emergence of variants of concern that can evade immune detection (PubMed: 33654012). These mutations often result in reduced binding affinity for certain therapeutic antibodies, necessitating the continuous development of new biologics. Monitoring the structural evolution of the RBM is vital for predicting the efficacy of current vaccines and guiding the design of next-generation boosters.

Other names

SARS-CoV-2 spike RBMReceptor-binding motif of SARS-CoV-2 spike proteinS-RBMSpike protein RBM

Neutralizing antibodies bind to the RBM to sterically hinder its interaction with the host Angiotensin-Converting Enzyme 2 (ACE2) receptor, thereby preventing viral entry into the host cell (PubMed: 32511539).