Studying SARS-CoV-2 interactions using phage-displayed receptor binding domain as a model protein
Abstract SARS-CoV-2 receptor binding domain (RBD) mediates viral entry into human cells through its interaction with angiotensin converting enzyme 2 (ACE2). Most neutralizing antibodies elicited by infection or vaccination target this domain. Such a functional relevance, together with large RBD sequ...
| Main Authors: | , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2024-01-01
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| Series: | Scientific Reports |
| Online Access: | https://doi.org/10.1038/s41598-023-50450-4 |
| _version_ | 1797363442024185856 |
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| author | Beatriz Pérez-Massón Yazmina Quintana-Pérez Yaima Tundidor Dayana Pérez-Martínez Camila Castro-Martínez Mario Pupo-Meriño Ivette Orosa Ernesto Relova-Hernández Rosmery Villegas Osmany Guirola Gertrudis Rojas |
| author_facet | Beatriz Pérez-Massón Yazmina Quintana-Pérez Yaima Tundidor Dayana Pérez-Martínez Camila Castro-Martínez Mario Pupo-Meriño Ivette Orosa Ernesto Relova-Hernández Rosmery Villegas Osmany Guirola Gertrudis Rojas |
| author_sort | Beatriz Pérez-Massón |
| collection | DOAJ |
| description | Abstract SARS-CoV-2 receptor binding domain (RBD) mediates viral entry into human cells through its interaction with angiotensin converting enzyme 2 (ACE2). Most neutralizing antibodies elicited by infection or vaccination target this domain. Such a functional relevance, together with large RBD sequence variability arising during viral spreading, point to the need of exploring the complex landscape of interactions between RBD-derived variants, ACE2 and antibodies. The current work was aimed at developing a simple platform to do so. Biologically active and antigenic Wuhan-Hu-1 RBD, as well as mutated RBD variants found in nature, were successfully displayed on filamentous phages. Mutational scanning confirmed the global plasticity of the receptor binding motif within RBD, highlighted residues playing a critical role in receptor binding, and identified mutations strengthening the interaction. The ability of vaccine-induced antibodies to inhibit ACE2 binding of many mutated RBD variants, albeit at different extents, was shown. Amino acid replacements which could compromise such inhibitory potential were underscored. The expansion of our approach could be the starting point for a large-scale phage-based exploration of diversity within RBD of SARS-CoV-2 and related coronaviruses, useful to understand structure–function relationships, to engineer RBD proteins, and to anticipate changes to watch during viral evolution. |
| first_indexed | 2024-03-08T16:20:23Z |
| format | Article |
| id | doaj.art-5fb8da803ded4e869e1bc185a4ff61c6 |
| institution | Directory Open Access Journal |
| issn | 2045-2322 |
| language | English |
| last_indexed | 2024-03-08T16:20:23Z |
| publishDate | 2024-01-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj.art-5fb8da803ded4e869e1bc185a4ff61c62024-01-07T12:22:38ZengNature PortfolioScientific Reports2045-23222024-01-0114111910.1038/s41598-023-50450-4Studying SARS-CoV-2 interactions using phage-displayed receptor binding domain as a model proteinBeatriz Pérez-Massón0Yazmina Quintana-Pérez1Yaima Tundidor2Dayana Pérez-Martínez3Camila Castro-Martínez4Mario Pupo-Meriño5Ivette Orosa6Ernesto Relova-Hernández7Rosmery Villegas8Osmany Guirola9Gertrudis Rojas10Center of Molecular ImmunologyCenter of Molecular ImmunologyCenter of Molecular ImmunologyCenter of Molecular ImmunologyCenter of Molecular ImmunologyUniversidad de Ciencias InformáticasCenter of Molecular ImmunologyCenter of Molecular ImmunologyUniversidad de Ciencias InformáticasCenter for Genetic Engineering and BiotechnologyCenter of Molecular ImmunologyAbstract SARS-CoV-2 receptor binding domain (RBD) mediates viral entry into human cells through its interaction with angiotensin converting enzyme 2 (ACE2). Most neutralizing antibodies elicited by infection or vaccination target this domain. Such a functional relevance, together with large RBD sequence variability arising during viral spreading, point to the need of exploring the complex landscape of interactions between RBD-derived variants, ACE2 and antibodies. The current work was aimed at developing a simple platform to do so. Biologically active and antigenic Wuhan-Hu-1 RBD, as well as mutated RBD variants found in nature, were successfully displayed on filamentous phages. Mutational scanning confirmed the global plasticity of the receptor binding motif within RBD, highlighted residues playing a critical role in receptor binding, and identified mutations strengthening the interaction. The ability of vaccine-induced antibodies to inhibit ACE2 binding of many mutated RBD variants, albeit at different extents, was shown. Amino acid replacements which could compromise such inhibitory potential were underscored. The expansion of our approach could be the starting point for a large-scale phage-based exploration of diversity within RBD of SARS-CoV-2 and related coronaviruses, useful to understand structure–function relationships, to engineer RBD proteins, and to anticipate changes to watch during viral evolution.https://doi.org/10.1038/s41598-023-50450-4 |
| spellingShingle | Beatriz Pérez-Massón Yazmina Quintana-Pérez Yaima Tundidor Dayana Pérez-Martínez Camila Castro-Martínez Mario Pupo-Meriño Ivette Orosa Ernesto Relova-Hernández Rosmery Villegas Osmany Guirola Gertrudis Rojas Studying SARS-CoV-2 interactions using phage-displayed receptor binding domain as a model protein Scientific Reports |
| title | Studying SARS-CoV-2 interactions using phage-displayed receptor binding domain as a model protein |
| title_full | Studying SARS-CoV-2 interactions using phage-displayed receptor binding domain as a model protein |
| title_fullStr | Studying SARS-CoV-2 interactions using phage-displayed receptor binding domain as a model protein |
| title_full_unstemmed | Studying SARS-CoV-2 interactions using phage-displayed receptor binding domain as a model protein |
| title_short | Studying SARS-CoV-2 interactions using phage-displayed receptor binding domain as a model protein |
| title_sort | studying sars cov 2 interactions using phage displayed receptor binding domain as a model protein |
| url | https://doi.org/10.1038/s41598-023-50450-4 |
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