Humanized single domain antibodies neutralize SARS-CoV-2 by targeting the spike receptor binding domain.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spreads worldwide and leads to an unprecedented medical burden and lives lost. Neutralizing antibodies provide efficient blockade for viral infection and are a promising category of biological therapies. Here, using SARS-CoV-2 spike receptor-binding domain (RBD) as a bait, we generate a panel of ...
humanized single domain antibodies (sdAbs) from a synthetic library. These sdAbs reveal binding kinetics with the equilibrium dissociation constant (KD) of 0.99-35.5?nM. The monomeric sdAbs show half maximal neutralization concentration (EC50) of 0.0009-0.07?µg/mL and 0.13-0.51?µg/mL against SARS-CoV-2 pseudotypes, and authentic SARS-CoV-2, respectively. Competitive ligand-binding experiments suggest that the sdAbs either completely block or significantly inhibit the association between SARS-CoV-2 RBD and viral entry receptor ACE2. Fusion of the human IgG1 Fc to sdAbs improve their neutralization activity by up to ten times. These results support neutralizing sdAbs as a potential alternative for antiviral therapies.
Mesh Terms:
Angiotensin-Converting Enzyme 2, Animals, Antibodies, Neutralizing, COVID-19, Chlorocebus aethiops, Coronavirus Infections, HEK293 Cells, Humans, Immunoglobulin G, Models, Molecular, Pandemics, Peptidyl-Dipeptidase A, Pneumonia, Viral, Protein Binding, Receptors, Virus, Single-Domain Antibodies, Spike Glycoprotein, Coronavirus, Vero Cells
Nat Commun
Date: Dec. 10, 2019
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