A neutralizing human antibody binds to the N-terminal domain of the Spike protein of SARS-CoV-2

Science. 2020 Aug 7;369(6504):650-655. doi: 10.1126/science.abc6952. Epub 2020 Jun 22.

Abstract

Developing therapeutics against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) could be guided by the distribution of epitopes, not only on the receptor binding domain (RBD) of the Spike (S) protein but also across the full Spike (S) protein. We isolated and characterized monoclonal antibodies (mAbs) from 10 convalescent COVID-19 patients. Three mAbs showed neutralizing activities against authentic SARS-CoV-2. One mAb, named 4A8, exhibits high neutralization potency against both authentic and pseudotyped SARS-CoV-2 but does not bind the RBD. We defined the epitope of 4A8 as the N-terminal domain (NTD) of the S protein by determining with cryo-eletron microscopy its structure in complex with the S protein to an overall resolution of 3.1 angstroms and local resolution of 3.3 angstroms for the 4A8-NTD interface. This points to the NTD as a promising target for therapeutic mAbs against COVID-19.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Angiotensin-Converting Enzyme 2
  • Animals
  • Antibodies, Monoclonal / blood
  • Antibodies, Monoclonal / chemistry
  • Antibodies, Monoclonal / immunology*
  • Antibodies, Monoclonal / metabolism
  • Antibodies, Neutralizing / blood
  • Antibodies, Neutralizing / chemistry
  • Antibodies, Neutralizing / immunology*
  • Antibodies, Neutralizing / metabolism
  • Antibodies, Viral / blood
  • Antibodies, Viral / chemistry
  • Antibodies, Viral / immunology*
  • Antibodies, Viral / metabolism
  • Antibody Affinity
  • Antibody Specificity
  • Antigens, Viral / immunology
  • B-Lymphocytes / immunology
  • Betacoronavirus / immunology*
  • COVID-19
  • Chlorocebus aethiops
  • Coronavirus Infections / immunology*
  • Coronavirus Infections / therapy
  • Coronavirus Nucleocapsid Proteins
  • Cryoelectron Microscopy
  • Enzyme-Linked Immunosorbent Assay
  • Genes, Immunoglobulin Heavy Chain
  • Humans
  • Immunologic Memory
  • Middle Aged
  • Mutation
  • Nucleocapsid Proteins / immunology
  • Pandemics
  • Peptidyl-Dipeptidase A / metabolism
  • Phosphoproteins
  • Pneumonia, Viral / immunology*
  • Pneumonia, Viral / therapy
  • Protein Domains
  • Protein Interaction Domains and Motifs / immunology
  • Receptors, Coronavirus
  • Receptors, Virus / metabolism
  • SARS-CoV-2
  • Spike Glycoprotein, Coronavirus / chemistry*
  • Spike Glycoprotein, Coronavirus / immunology*
  • Spike Glycoprotein, Coronavirus / metabolism
  • Vero Cells
  • Young Adult

Substances

  • Antibodies, Monoclonal
  • Antibodies, Neutralizing
  • Antibodies, Viral
  • Antigens, Viral
  • Coronavirus Nucleocapsid Proteins
  • Nucleocapsid Proteins
  • Phosphoproteins
  • Receptors, Coronavirus
  • Receptors, Virus
  • Spike Glycoprotein, Coronavirus
  • nucleocapsid phosphoprotein, SARS-CoV-2
  • spike protein, SARS-CoV-2
  • Peptidyl-Dipeptidase A
  • ACE2 protein, human
  • Angiotensin-Converting Enzyme 2