Abstract
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is responsible for millions of infections and hundreds of thousands of deaths globally. There are no widely available licensed therapeutics against SARS-CoV-2, highlighting an urgent need for effective interventions. The virus enters host cells through binding of a receptor-binding domain within its trimeric spike glycoprotein to human angiotensin-converting enzyme 2. In this article, we describe the generation and characterization of a panel of murine mAbs directed against the receptor-binding domain. One mAb, 2B04, neutralized wild-type SARS-CoV-2 in vitro with remarkable potency (half-maximal inhibitory concentration of <2 ng/ml). In a murine model of SARS-CoV-2 infection, 2B04 protected challenged animals from weight loss, reduced lung viral load, and blocked systemic dissemination. Thus, 2B04 is a promising candidate for an effective antiviral that can be used to prevent SARS-CoV-2 infection.
Copyright © 2020 by The American Association of Immunologists, Inc.
Publication types
- Research Support, N.I.H., Extramural
MeSH terms
- Angiotensin-Converting Enzyme 2
- Animals
- Antibodies, Monoclonal / immunology
- Antibodies, Monoclonal / pharmacology
- Antibodies, Monoclonal / therapeutic use*
- Antibodies, Neutralizing / immunology
- Antibodies, Neutralizing / pharmacology
- Antibodies, Neutralizing / therapeutic use*
- Antibodies, Viral / immunology
- Antibodies, Viral / pharmacology
- Antibodies, Viral / therapeutic use*
- Betacoronavirus / drug effects*
- COVID-19
- Chlorocebus aethiops
- Coronavirus Infections / drug therapy*
- Coronavirus Infections / immunology*
- Coronavirus Infections / virology
- Disease Models, Animal
- Epitope Mapping
- Female
- HEK293 Cells
- Humans
- Immunodominant Epitopes / immunology
- Mice
- Mice, Inbred C57BL
- Pandemics
- Peptidyl-Dipeptidase A / genetics
- Peptidyl-Dipeptidase A / metabolism
- Pneumonia, Viral / drug therapy*
- Pneumonia, Viral / immunology*
- Pneumonia, Viral / virology
- Protein Interaction Domains and Motifs / genetics
- Protein Interaction Domains and Motifs / immunology
- SARS-CoV-2
- Spike Glycoprotein, Coronavirus / chemistry
- Spike Glycoprotein, Coronavirus / metabolism
- Transfection
- Vero Cells
Substances
- Antibodies, Monoclonal
- Antibodies, Neutralizing
- Antibodies, Viral
- Immunodominant Epitopes
- Spike Glycoprotein, Coronavirus
- spike protein, SARS-CoV-2
- Peptidyl-Dipeptidase A
- ACE2 protein, human
- Ace2 protein, mouse
- Angiotensin-Converting Enzyme 2