Structural insights into antibody-mediated neutralization of SARS-CoV-2

Abstract

In less than a year, researchers have uncovered structure–function details for many of the proteins encoded by SARS-CoV-2. We report structures that reveal how monoclonal neutralizing antibodies bind spike to prevent infection. One such monoclonal antibody, BG10–19, targets a highly-conserved, proteoglycan epitope on the SARS-CoV-2 RBD, which sits outside of mutated residue positions found in all circulating variants of concern (i.e. alpha, beta, gamma, delta, kappa, and lambda). In addition, BG10–19 bridges adjacent RBDs and locks the spike trimer in a completely closed conformation to potently neutralize SARSCoV-2 and heterologous SARS-like coronaviruses. Thus, BG10–19 is a candidate antibody therapeutic to combat continuing SARS-CoV-2 antigenic drift and represents an attractive epitope for pan-sarbecovirus vaccine design.