Potent Neutralizing Antibodies Directed to Multiple Epitopes on SARS-CoV-2 Spike

Abstract

The SARS-CoV-2 pandemic rages on with devasting consequences not only on human lives but also on the global economy. The discovery and development of virus-neutralizing monoclonal antibodies may be one approach that could be used to treat or prevent infection by this novel coronavirus. Herein we report the isolation of 61 SARS-CoV-2-neutralizing monoclonal antibodies from memory B cells in the blood of 5 infected patients hospitalized with severe disease. Among these are 19 antibodies that potently neutralized the authentic SARS-CoV-2 in vitro, 9 of which exhibited exquisite potency, with 50% virus-inhibitory concentrations of 1 to 9 ng/mL. Epitope mapping and three cryo-electron-microscopy structures show that this collection of 19 antibodies not only includes numerous antibodies directed to the receptor-binding domain but also many directed to the N-terminal domain, indicating that both of these regions at the top of the viral spike are quite immunogenic. In addition, two other powerful neutralizing antibodies recognize quaternary epitopes that are proximal to and overlapping with the domains at the top of the spike. Several of these monoclonal antibodies are promising candidates for clinical development as potential therapeutic and/or prophylactic agents against SARS-CoV-2.