Abstract
Rapid design, screening, and characterization of biorecognition elements (BREs) is essential for the development of diagnostic tests and antiviral therapeutics needed to combat the spread of viruses such as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). To address this need, we developed a high-throughput pipeline combining in silico design of a peptide library specific for SARS-CoV-2 spike (S) protein and microarray screening to identify binding sequences. Our optimized microarray platform allowed the simultaneous screening of ~ 2.5 k peptides and rapid identification of binding sequences resulting in selection of four peptides with nanomolar affinity to the SARS-CoV-2 S protein. Finally, we demonstrated the successful integration of one of the top peptides into an electrochemical sensor with a clinically relevant limit of detection for S protein in spiked saliva. Our results demonstrate the utility of this novel pipeline for the selection of peptide BREs in response to the SARS-CoV-2 pandemic, and the broader application of such a platform in response to future viral threats.
Highlights
Rapid design, screening, and characterization of biorecognition elements (BREs) is essential for the development of diagnostic tests and antiviral therapeutics needed to combat the spread of viruses such as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)
SARS-CoV-2 entry into host cells is facilitated by the S protein’s receptor binding domain (RBD) located on the S1 subunit, which binds to the angiotensin-converting enzyme 2 (ACE2) receptor located on epithelial cells lining the respiratory tract[8]
Analysis of the neutralizing sites on the SARS-CoV-2 S protein indicated that most monoclonal antibodies targeted the receptor binding domain (RBD) of the S p rotein[25,26], while only one targeted the N-terminal domain (NTD)[27]
Summary
Rapid design, screening, and characterization of biorecognition elements (BREs) is essential for the development of diagnostic tests and antiviral therapeutics needed to combat the spread of viruses such as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). To address this need, we developed a high-throughput pipeline combining in silico design of a peptide library specific for SARS-CoV-2 spike (S) protein and microarray screening to identify binding sequences. SARS-CoV-2 entry into host cells is facilitated by the S protein’s receptor binding domain (RBD) located on the S1 subunit, which binds to the angiotensin-converting enzyme 2 (ACE2) receptor located on epithelial cells lining the respiratory tract[8] Viral surface proteins, such as the S protein, are promising targets for both virus detection and neutralization. The combination of computational peptide design and microarray screening has not been previously reported for viral protein targets
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