Antibody-like proteins that capture and neutralize SARS-CoV-2

Sci Adv. 2020 Oct 14;6(42):eabd3916. doi: 10.1126/sciadv.abd3916. Print 2020 Oct.

Abstract

To combat severe acute respiratory syndrome-related coronavirus 2 (SARS-CoV-2) and any unknown emerging pathogens in the future, the development of a rapid and effective method to generate high-affinity antibodies or antibody-like proteins is of critical importance. We here report high-speed in vitro selection of multiple high-affinity antibody-like proteins against various targets including the SARS-CoV-2 spike protein. The sequences of monobodies against the SARS-CoV-2 spike protein were successfully procured within only 4 days. Furthermore, the obtained monobody efficiently captured SARS-CoV-2 particles from the nasal swab samples of patients and exhibited a high neutralizing activity against SARS-CoV-2 infection (half-maximal inhibitory concentration, 0.5 nanomolar). High-speed in vitro selection of antibody-like proteins is a promising method for rapid development of a detection method for, and of a neutralizing protein against, a virus responsible for an ongoing, and possibly a future, pandemic.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Angiotensin-Converting Enzyme 2
  • Antibodies, Immobilized / chemistry
  • Antibodies, Immobilized / immunology
  • Antibodies, Neutralizing / chemistry
  • Antibodies, Neutralizing / immunology
  • Antibodies, Neutralizing / metabolism
  • Betacoronavirus / genetics
  • Betacoronavirus / immunology*
  • Betacoronavirus / isolation & purification
  • COVID-19
  • Cell Surface Display Techniques / methods
  • Coronavirus Infections / pathology
  • Coronavirus Infections / virology
  • Dimerization
  • Humans
  • Kinetics
  • Pandemics
  • Peptides / chemistry
  • Peptides / immunology
  • Peptidyl-Dipeptidase A / chemistry
  • Peptidyl-Dipeptidase A / immunology*
  • Peptidyl-Dipeptidase A / metabolism
  • Pneumonia, Viral / pathology
  • Pneumonia, Viral / virology
  • Protein Domains / immunology
  • Protein Subunits / chemistry
  • Protein Subunits / immunology
  • Protein Subunits / metabolism
  • RNA, Viral / metabolism
  • SARS-CoV-2
  • Single-Domain Antibodies / chemistry
  • Single-Domain Antibodies / immunology*
  • Single-Domain Antibodies / metabolism
  • Spike Glycoprotein, Coronavirus / chemistry
  • Spike Glycoprotein, Coronavirus / immunology*

Substances

  • Antibodies, Immobilized
  • Antibodies, Neutralizing
  • Peptides
  • Protein Subunits
  • RNA, Viral
  • Single-Domain Antibodies
  • Spike Glycoprotein, Coronavirus
  • spike protein, SARS-CoV-2
  • Peptidyl-Dipeptidase A
  • ACE2 protein, human
  • Angiotensin-Converting Enzyme 2