Neutralizing antibodies targeting the SARS-CoV-2 receptor binding domain isolated from a naive human antibody library.

Infection with SARS-CoV-2 elicits robust antibody responses in some patients, with a majority of the response directed at the receptor binding domain (RBD) of the spike surface glycoprotein. Remarkably, many patient-derived antibodies that potently inhibit viral infection harbor few to no mutations from the germline, suggesting that naive antibody libraries ...
are a viable means for discovery of novel SARS-CoV-2 neutralizing antibodies. Here, we used a yeast surface-display library of human naive antibodies to isolate and characterize three novel neutralizing antibodies that target the RBD: one that blocks interaction with angiotensin-converting enzyme 2 (ACE2), the human receptor for SARS-CoV-2, and two that target other epitopes on the RBD. These three antibodies neutralized SARS-CoV-2 spike-pseudotyped lentivirus with IC50 values as low as 60?ng/ml in vitro. Using a biolayer interferometry-based binding competition assay, we determined that these antibodies have distinct but overlapping epitopes with antibodies elicited during natural COVID-19 infection. Taken together, these analyses highlight how in vitro selection of naive antibodies can mimic the humoral response in vivo, yielding neutralizing antibodies and various epitopes that can be effectively targeted on the SARS-CoV-2 RBD.
Mesh Terms:
Angiotensin-Converting Enzyme 2, Antibodies, Neutralizing, Binding Sites, COVID-19, Epitopes, Humans, Molecular Docking Simulation, Protein Binding, Protein Interaction Domains and Motifs, SARS-CoV-2, Spike Glycoprotein, Coronavirus
Protein Sci
Date: Dec. 01, 2020
Download Curated Data For This Publication
Switch View:
  • Interactions 1