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TitlePotent Neutralizing Antibodies Directed to Multiple Epitopes on SARS-CoV-2 Spike.
Journal, issue, pagesbioRxiv, Year 2020
Publish dateJul 16, 2020
PubMed AbstractThe SARS-CoV-2 pandemic rages on with devasting consequences on human lives and the global economy . The discovery and development of virus-neutralizing monoclonal antibodies could be one approach ...The SARS-CoV-2 pandemic rages on with devasting consequences on human lives and the global economy . The discovery and development of virus-neutralizing monoclonal antibodies could be one approach to treat or prevent infection by this novel coronavirus. Here we report the isolation of 61 SARS-CoV-2-neutralizing monoclonal antibodies from 5 infected patients hospitalized with severe disease. Among these are 19 antibodies that potently neutralized the authentic SARS-CoV-2 , 9 of which exhibited exquisite potency, with 50% virus-inhibitory concentrations of 0.7 to 9 ng/mL. Epitope mapping showed this collection of 19 antibodies to be about equally divided between those directed to the receptor-binding domain (RBD) and those to the N-terminal domain (NTD), indicating that both of these regions at the top of the viral spike are immunogenic. In addition, two other powerful neutralizing antibodies recognized quaternary epitopes that are overlapping with the domains at the top of the spike. Cryo-electron microscopy reconstructions of one antibody targeting RBD, a second targeting NTD, and a third bridging two separate RBDs revealed recognition of the closed, "all RBD-down" conformation 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.
External linksbioRxiv / PubMed:32587975 / PubMed Central
MethodsEM (single particle)
Resolution3.9 - 5.8 Å
Structure data

EMDB-22158:
Cryo-EM structure of the SARS-CoV-2 spike glycoprotein in the RBD up conformation bound to Fab 4-8
Method: EM (single particle) / Resolution: 4.0 Å

EMDB-22159:
Cryo-EM structure of the SARS-CoV-2 spike glycoprotein in the RBD down conformation and Fab 4-8
Method: EM (single particle) / Resolution: 3.9 Å

EMDB-22275:
Cryo-EM structure of the SARS-CoV-2 spike glycoprotein bound to Fab 2-43
Method: EM (single particle) / Resolution: 5.8 Å

Source
  • Severe acute respiratory syndrome coronavirus 2

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