Chimeric peptides targeting the receptor-binding domain of SARS-CoV-2 variants inhibit ACE2 interaction
Issued Date
2025-03-01
Resource Type
ISSN
0125877X
Scopus ID
2-s2.0-105001219183
Pubmed ID
39580631
Journal Title
Asian Pacific journal of allergy and immunology
Volume
43
Issue
1
Start Page
124
End Page
134
Rights Holder(s)
SCOPUS
Bibliographic Citation
Asian Pacific journal of allergy and immunology Vol.43 No.1 (2025) , 124-134
Suggested Citation
Ubonsri P., Panmanee J., Meewan I., Masrinoul P., Komaikul J., Piboonpocanun S. Chimeric peptides targeting the receptor-binding domain of SARS-CoV-2 variants inhibit ACE2 interaction. Asian Pacific journal of allergy and immunology Vol.43 No.1 (2025) , 124-134. 134. doi:10.12932/AP-030424-1833 Retrieved from: https://repository.li.mahidol.ac.th/handle/123456789/109308
Title
Chimeric peptides targeting the receptor-binding domain of SARS-CoV-2 variants inhibit ACE2 interaction
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Corresponding Author(s)
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Abstract
BACKGROUND: The receptor-binding domain (RBD) of the SARS-CoV-2 spike (S) protein is pivotal in facilitating viral entry and serves as a major target for vaccine development and therapeutics. Despite undergoing mutations aimed at evading host immunity, certain regions within the RBD remain conserved. OBJECTIVE: This study aimed to identify peptides capable of interacting with these conserved regions of the RBD across various variants and assess their neutralization potential. METHODS: The PhD-12 phage display library underwent screening to identify phages binding to the RBD. Selected phage clones were examined for binding to the RBD of multiple variants, including 2019-nCoV, Delta (B.1.617.2), Omicron (B.1.1.529), and XBB. Peptides, expressed as chimeric constructs, were tested for their binding to the RBD, the Omicron trimeric S, inactivated SARS-CoV-2 virus, and neutralizing activity. The binding sites were analyzed using Molecular Docking. RESULTS: Two selected phage clones displayed peptides binding to the RBD of multiple variants. Chimeric T hioredoxin-peptides (Trx-RB9 and Trx-RB10) exhibited binding to both inactivated SARS-CoV-2 and the Omicron trimeric S, with half-maximum effective concentrations (EC50 ) values of 111.9 and 360.2 nM, respectively. Molecular docking revealed distinct binding sites within the RBD of the Omicron trimeric S for both Trx-RB9 and Trx-RB10. A mixture of Trx-RB9 and Trx-RB10 inhibited 78% of the binding of recombinant human ACE2 to the Omicron trimeric S. CONCLUSIONS: The chimeric Trx-RB9 and Trx-RB10 peptides bind to the RBD of SARS-CoV-2 variants and inhibit the binding of ACE2 to the RBD of the Omicron trimeric S.