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

T Kondo; Y Iwatani; K Matsuoka; T Fujino; S Umemoto; Y Yokomaku; K Ishizaki; S Kito; T Sezaki; G Hayashi; H Murakami

doi:10.1126/sciadv.abd3916

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.

Authors

T Kondo¹, Y Iwatani^{2

3}, K Matsuoka², T Fujino¹, S Umemoto¹, Y Yokomaku², K Ishizaki¹, S Kito¹, T Sezaki¹, G Hayashi^{1

4}, H Murakami^{5

6}

Affiliations

¹ Department of Biomolecular Engineering, Graduate School of Engineering, Nagoya University, Nagoya, Japan.
² Department of Infectious Diseases and Immunology, Clinical Research Center, National Hospital Organization Nagoya Medical Center, Nagoya, Japan.
³ Division of Basic Medicine, Graduate School of Medicine, Nagoya University, Nagoya, Japan.
⁴ Japan Science and Technology Agency (JST), PRESTO, Saitama, Japan.
⁵ Department of Biomolecular Engineering, Graduate School of Engineering, Nagoya University, Nagoya, Japan. murah@chembio.nagoya-u.ac.jp.
⁶ Institute of Nano-Life-Systems, Institutes of Innovation for Future Society, Nagoya University, Nagoya, Japan.

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.

Copyright © 2020 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution NonCommercial License 4.0 (CC BY-NC).

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