Synthetic carbohydrate-binding agents neutralize SARS-CoV-2 by inhibiting binding of the spike protein to ACE2
Summary: Developing strategies against the SARS-CoV-2 is currently a main research subject. SARS-CoV-2 infects host cells by binding to human ACE2 receptors. Both, virus and ACE2, are highly glycosylated, and exploiting glycans of the SARS-CoV-2 envelope as binding sites for ACE2 represents a virus...
| Main Authors: | , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2022-05-01
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| Series: | iScience |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2589004222005090 |
| _version_ | 1811339895890771968 |
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| author | Oscar Francesconi Lorena Donnici Marco Fragai Elisa Pesce Mauro Bombaci Alessandra Fasciani Lara Manganaro Matteo Conti Renata Grifantini Raffaele De Francesco Cristina Nativi Stefano Roelens |
| author_facet | Oscar Francesconi Lorena Donnici Marco Fragai Elisa Pesce Mauro Bombaci Alessandra Fasciani Lara Manganaro Matteo Conti Renata Grifantini Raffaele De Francesco Cristina Nativi Stefano Roelens |
| author_sort | Oscar Francesconi |
| collection | DOAJ |
| description | Summary: Developing strategies against the SARS-CoV-2 is currently a main research subject. SARS-CoV-2 infects host cells by binding to human ACE2 receptors. Both, virus and ACE2, are highly glycosylated, and exploiting glycans of the SARS-CoV-2 envelope as binding sites for ACE2 represents a virus strategy for attacking the human host. We report here that a family of mannose-binding synthetic carbohydrate-binding agents (CBAs) inhibits SARS-CoV-2 infection, showing broad neutralizing activity vs. several variants of the spike protein. Preliminary tests indicated that the investigated CBAs interact with the spike protein rather than with ACE2. For a lead compound (IDS060), which has been selected among others for its lack of cytotoxicity, evidence of binding to the RBD of the spike protein has been found by NMR experiments, while competitive binding assays in the presence of IDS060 showed inhibition of binding of RBD to hACE2, although neutralizing activity was also observed with variants showing reduced or depleted binding. |
| first_indexed | 2024-04-13T18:34:14Z |
| format | Article |
| id | doaj.art-714c1c36152045e78a22d088d37e8025 |
| institution | Directory Open Access Journal |
| issn | 2589-0042 |
| language | English |
| last_indexed | 2024-04-13T18:34:14Z |
| publishDate | 2022-05-01 |
| publisher | Elsevier |
| record_format | Article |
| series | iScience |
| spelling | doaj.art-714c1c36152045e78a22d088d37e80252022-12-22T02:34:58ZengElsevieriScience2589-00422022-05-01255104239Synthetic carbohydrate-binding agents neutralize SARS-CoV-2 by inhibiting binding of the spike protein to ACE2Oscar Francesconi0Lorena Donnici1Marco Fragai2Elisa Pesce3Mauro Bombaci4Alessandra Fasciani5Lara Manganaro6Matteo Conti7Renata Grifantini8Raffaele De Francesco9Cristina Nativi10Stefano Roelens11Dipartimento di Chimica, DICUS, University of Florence, Florence, ItalyFondazione INGM - Istituto Nazionale Genetica Molecolare “Romeo ed Enrica Invernizzi”, Milan, ItalyDipartimento di Chimica, DICUS, University of Florence, Florence, Italy; CERM, University of Florence, Florence, ItalyFondazione INGM - Istituto Nazionale Genetica Molecolare “Romeo ed Enrica Invernizzi”, Milan, ItalyFondazione INGM - Istituto Nazionale Genetica Molecolare “Romeo ed Enrica Invernizzi”, Milan, ItalyFondazione INGM - Istituto Nazionale Genetica Molecolare “Romeo ed Enrica Invernizzi”, Milan, ItalyFondazione INGM - Istituto Nazionale Genetica Molecolare “Romeo ed Enrica Invernizzi”, Milan, Italy; Dipartimento di Scienze Farmacologiche e Biomolecolari, University of Milan, Milan, ItalyFondazione INGM - Istituto Nazionale Genetica Molecolare “Romeo ed Enrica Invernizzi”, Milan, ItalyFondazione INGM - Istituto Nazionale Genetica Molecolare “Romeo ed Enrica Invernizzi”, Milan, Italy; Corresponding authorFondazione INGM - Istituto Nazionale Genetica Molecolare “Romeo ed Enrica Invernizzi”, Milan, Italy; Dipartimento di Scienze Farmacologiche e Biomolecolari, University of Milan, Milan, Italy; Corresponding authorDipartimento di Chimica, DICUS, University of Florence, Florence, Italy; Corresponding authorINSTM, University of Florence, Florence, ItalySummary: Developing strategies against the SARS-CoV-2 is currently a main research subject. SARS-CoV-2 infects host cells by binding to human ACE2 receptors. Both, virus and ACE2, are highly glycosylated, and exploiting glycans of the SARS-CoV-2 envelope as binding sites for ACE2 represents a virus strategy for attacking the human host. We report here that a family of mannose-binding synthetic carbohydrate-binding agents (CBAs) inhibits SARS-CoV-2 infection, showing broad neutralizing activity vs. several variants of the spike protein. Preliminary tests indicated that the investigated CBAs interact with the spike protein rather than with ACE2. For a lead compound (IDS060), which has been selected among others for its lack of cytotoxicity, evidence of binding to the RBD of the spike protein has been found by NMR experiments, while competitive binding assays in the presence of IDS060 showed inhibition of binding of RBD to hACE2, although neutralizing activity was also observed with variants showing reduced or depleted binding.http://www.sciencedirect.com/science/article/pii/S2589004222005090Biological sciencesCarbohydrateMicrobiology |
| spellingShingle | Oscar Francesconi Lorena Donnici Marco Fragai Elisa Pesce Mauro Bombaci Alessandra Fasciani Lara Manganaro Matteo Conti Renata Grifantini Raffaele De Francesco Cristina Nativi Stefano Roelens Synthetic carbohydrate-binding agents neutralize SARS-CoV-2 by inhibiting binding of the spike protein to ACE2 iScience Biological sciences Carbohydrate Microbiology |
| title | Synthetic carbohydrate-binding agents neutralize SARS-CoV-2 by inhibiting binding of the spike protein to ACE2 |
| title_full | Synthetic carbohydrate-binding agents neutralize SARS-CoV-2 by inhibiting binding of the spike protein to ACE2 |
| title_fullStr | Synthetic carbohydrate-binding agents neutralize SARS-CoV-2 by inhibiting binding of the spike protein to ACE2 |
| title_full_unstemmed | Synthetic carbohydrate-binding agents neutralize SARS-CoV-2 by inhibiting binding of the spike protein to ACE2 |
| title_short | Synthetic carbohydrate-binding agents neutralize SARS-CoV-2 by inhibiting binding of the spike protein to ACE2 |
| title_sort | synthetic carbohydrate binding agents neutralize sars cov 2 by inhibiting binding of the spike protein to ace2 |
| topic | Biological sciences Carbohydrate Microbiology |
| url | http://www.sciencedirect.com/science/article/pii/S2589004222005090 |
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