De Novo Discovery of High-Affinity Peptide Binders for the SARS-CoV-2 Spike Protein

Sebastian Pomplun, Muhammad Jbara, Anthony J. Quartararo, Genwei Zhang, Joseph S. Brown, Yen Chun Lee, Xiyun Ye, Stephanie Hanna, Bradley L. Pentelute

研究成果: Article同行評審

60 引文 斯高帕斯(Scopus)


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.

頁(從 - 到)156-163
期刊ACS Central Science
出版狀態Published - 2021 1月 27

All Science Journal Classification (ASJC) codes

  • 一般化學
  • 一般化學工程


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