De Novo Discovery of High-Affinity Peptide Binders for the SARS-CoV-2 Spike Protein
Author(s)
Pomplun, Sebastian Johannes; Jbara, Muhammad; Quartararo, Anthony James; Zhang, Genwei; Brown, Joseph S.; Lee, Yen-Chun; Ye, Xiyun; Hanna, Stephanie; Pentelute, Bradley L.; ... Show more Show less
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The β-coronavirus SARS-CoV-2 has caused a global pandemic. Affinity reagents targeting the SARS-CoV-2 spike protein are of interest for the development of therapeutics and diagnostics. We used affinity selection-mass spectrometry for the rapid discovery of synthetic high-affinity peptide binders for the receptor binding domain (RBD) of the SARS-CoV-2 spike protein. From library screening with 800 million synthetic peptides, we identified three sequences with nanomolar affinities (dissociation constants Kd = 80-970 nM) for RBD and selectivity over human serum proteins. Nanomolar RBD concentrations in a biological matrix could be detected using the biotinylated lead peptide in ELISA format. These peptides do not compete for ACE2 binding, and their site of interaction on the SARS-CoV-2-spike-RBD might be unrelated to the ACE2 binding site, making them potential orthogonal reagents for sandwich immunoassays. These findings serve as a starting point for the development of SARS-CoV-2 diagnostics or conjugates for virus-directed delivery of therapeutics.
Date issued
2020-12Department
Massachusetts Institute of Technology. Department of ChemistryJournal
ACS Central Science
Publisher
American Chemical Society (ACS)
Citation
Pomplun, Sebastian et al. "De Novo Discovery of High-Affinity Peptide Binders for the SARS-CoV-2 Spike Protein." ACS Central Science 7, 1 (December 2020): 156–163 © 2020 American Chemical Society
Version: Final published version
ISSN
2374-7943
2374-7951