Open AccessDe Novo Discovery of High-Affinity Peptide Binders for the SARS-CoV-2 Spike Protein
Author(s) -
Sebastian Pomplun,
Muhammad Jbara,
Anthony J. Quartararo,
Genwei Zhang,
Joseph S. Brown,
YenChun Lee,
Xiyun Ye,
Stephanie Hanna,
Bradley L. Pentelute
Publication year - 2020
Publication title -
acs central science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.893
H-Index - 76
eISSN - 2374-7951
pISSN - 2374-7943
DOI - 10.1021/acscentsci.0c01309
Subject(s) - biotinylation , peptide , chemistry , covid-19 , peptide library , dissociation constant , coronavirus , computational biology , biochemistry , combinatorial chemistry , microbiology and biotechnology , peptide sequence , biology , receptor , infectious disease (medical specialty) , medicine , disease , pathology , gene
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 K d = 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.