SARS-CoV-2 spike glycoprotein receptor-binding domain – lateral allosteric epitope

The SARS-CoV-2 spike glycoprotein receptor-binding domain (RBD) lateral allosteric epitope is a highly conserved antigenic site located on the side of the RBD, distinct from the receptor-binding motif (RBM). This epitope is primarily targeted by Class 3 neutralizing antibodies, such as Sotrovimab (S309) and Bebtelovimab, which bind to the RBD in both its up and down conformations. Unlike antibodies that directly compete with the ACE2 receptor at the RBM, those targeting the lateral allosteric epitope exert their neutralizing effect through allosteric mechanisms, such as stabilizing the inactive down state or inducing structural changes that indirectly impair ACE2 binding. Because this region is less prone to mutations than the RBM, it serves as a critical target for developing broadly neutralizing therapeutics capable of maintaining activity against diverse viral variants. Drugs interacting with this site are used to treat COVID-19 by preventing viral entry into host cells and reducing viral load.

Other names

Class 3 RBD epitopeS309 epitopeLateral RBD epitopeConserved RBD allosteric siteSCORE-A epitope

Allosteric inhibition of ACE2 receptor binding by stabilizing the RBD in a down or inactive conformation and inducing conformational changes that impair receptor engagement.