Identifying Epitope Sites on the Receptor Binding Domain (RBD) of SARS-CoV-2

Abstract COVID-19 and SARS-CoV-2 variants continue to threaten human health life worldwide. Thousands of structures related have been rapidly determined, either by X-ray crystallography or CryoEM deposited in the Protein Data Bank (PDB) since 2020. Here, we systematically investigated 302 antibodies 78 nanobodies complex with spike protein receptor binding domain (RBD) SARS-CoV-2. We identified 23 common epitopic sites (ES) on RBD surface revealed vital role complementarity-determining Region (CDR) loops recognizing epitopes. The ES are characterized according secondary structure feature accessible area. About 75% total areas could access elicited antibodies, while CDR3 occupied 50% contact surface. analysis paratope-epitope (antibody-antigen) interaction based these epitope features potent neutralizing virus unique usage amino acids antibody. clustering antibody biophysical properties area availabilities found many motifs. Remarkably, most concern (VOC) escape mutations, including Omicron occur within ES. This not only explains differential ability recognize but also offers predictive guidelines for understanding that accumulated SARS mutations might play from immunogens. structural characterization epitope-paratope interactions provides insights structure-based vaccine design therapeutic strategies drugs against future virus.