Identification of SARS-CoV RBD-targeting monoclonal antibodies with cross-reactive or neutralizing activity against SARS-CoV-2

Wanbo Tai; Xiujuan Zhang; Yuxian He; Shibo Jiang; Lanying Du

doi:10.1016/j.antiviral.2020.104820

Identification of SARS-CoV RBD-targeting monoclonal antibodies with cross-reactive or neutralizing activity against SARS-CoV-2

Antiviral Res. 2020 Jul:179:104820. doi: 10.1016/j.antiviral.2020.104820. Epub 2020 May 13.

Authors

Wanbo Tai¹, Xiujuan Zhang¹, Yuxian He², Shibo Jiang³, Lanying Du⁴

Affiliations

¹ Lindsley F. Kimball Research Institute, New York Blood Center, New York, NY, 10065, USA.
² Institute of Pathogen Biology and Center for AIDS Research, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100730, China.
³ Lindsley F. Kimball Research Institute, New York Blood Center, New York, NY, 10065, USA; Key Laboratory of Medical Molecular Virology (MOE/NHC/CAMS), School of Basic Medical Sciences, Fudan University, Shanghai, 200032, China. Electronic address: [email protected].
⁴ Lindsley F. Kimball Research Institute, New York Blood Center, New York, NY, 10065, USA. Electronic address: [email protected].

Abstract

SARS-CoV-2-caused COVID-19 cases are growing globally, calling for developing effective therapeutics to control the current pandemic. SARS-CoV-2 and SARS-CoV recognize angiotensin-converting enzyme 2 (ACE2) receptor via the receptor-binding domain (RBD). Here, we identified six SARS-CoV RBD-specific neutralizing monoclonal antibodies (nAbs) that cross-reacted with SARS-CoV-2 RBD, two of which, 18F3 and 7B11, neutralized SARS-CoV-2 infection. 18F3 recognized conserved epitopes on SARS-CoV and SARS-CoV-2 RBDs, whereas 7B11 recognized epitopes on SARS-CoV RBD not fully conserved in SARS-CoV-2 RBD. The 18F3-recognizing epitopes on RBD did not overlap with the ACE2-binding sites, whereas those recognized by 7B11 were close to the ACE2-binding sites, explaining why 7B11 could, but 18F3 could not, block SARS-CoV or SARS-CoV-2 RBD binding to ACE2 receptor. Our study provides an alternative approach to prevent SARS-CoV-2 infection using anti-SARS-CoV nAbs.

Keywords: COVID-19; Cross-neutralization; Neutralizing monoclonal antibodies; Receptor-binding domain; SARS-CoV; SARS-CoV-2.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

MeSH terms

Amino Acid Sequence
Angiotensin-Converting Enzyme 2
Antibodies, Monoclonal / immunology*
Antibodies, Monoclonal / isolation & purification
Antibodies, Neutralizing / immunology*
Antibodies, Viral / immunology
Antigens, Viral / chemistry
Antigens, Viral / genetics
Antigens, Viral / immunology
Betacoronavirus / genetics
Betacoronavirus / immunology*
Binding Sites
COVID-19
Coronavirus Infections / virology*
Cross Reactions
Epitopes / immunology
HEK293 Cells
Humans
Neutralization Tests
Pandemics
Peptidyl-Dipeptidase A / immunology
Pneumonia, Viral / virology*
SARS-CoV-2
Severe acute respiratory syndrome-related coronavirus / genetics
Severe acute respiratory syndrome-related coronavirus / immunology*
Spike Glycoprotein, Coronavirus / chemistry
Spike Glycoprotein, Coronavirus / genetics
Spike Glycoprotein, Coronavirus / immunology*

Substances

Antibodies, Monoclonal
Antibodies, Neutralizing
Antibodies, Viral
Antigens, Viral
Epitopes
Spike Glycoprotein, Coronavirus
spike glycoprotein, SARS-CoV
Peptidyl-Dipeptidase A
ACE2 protein, human
Angiotensin-Converting Enzyme 2

Abstract

Publication types

MeSH terms

Substances

Grants and funding