Ultrapotent human antibodies protect against SARS-CoV-2 challenge via multiple mechanisms.

Efficient therapeutic options are needed to control the spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that has caused more than 922,000 fatalities as of 13 September 2020. We report the isolation and characterization of two ultrapotent SARS-CoV-2 human neutralizing antibodies (S2E12 and S2M11) that protect hamsters against SARS-CoV-2 ...
challenge. Cryo-electron microscopy structures show that S2E12 and S2M11 competitively block angiotensin-converting enzyme 2 (ACE2) attachment and that S2M11 also locks the spike in a closed conformation by recognition of a quaternary epitope spanning two adjacent receptor-binding domains. Antibody cocktails that include S2M11, S2E12, or the previously identified S309 antibody broadly neutralize a panel of circulating SARS-CoV-2 isolates and activate effector functions. Our results pave the way to implement antibody cocktails for prophylaxis or therapy, circumventing or limiting the emergence of viral escape mutants.
Mesh Terms:
Amino Acid Motifs, Angiotensin-Converting Enzyme 2, Animals, Antibodies, Neutralizing, Antibodies, Viral, Betacoronavirus, CHO Cells, COVID-19, Coronavirus Infections, Cricetinae, Cricetulus, Cryoelectron Microscopy, HEK293 Cells, Humans, Immunodominant Epitopes, Microscopy, Electron, Pandemics, Peptidyl-Dipeptidase A, Pneumonia, Viral, Protein Domains, SARS-CoV-2, Spike Glycoprotein, Coronavirus
Science
Date: Nov. 20, 2020
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