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 inves- tigated 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 cytotox- icity, 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.

Synthetic carbohydrate-binding agents neutralize SARS-CoV-2 by inhibiting binding of the spike protein to ACE2 / Oscar Francesconi, Cristina Nativi, Stefano Roelens. - In: ISCIENCE. - ISSN 2589-0042. - STAMPA. - 25:(2022), pp. 104239-104256.

Synthetic carbohydrate-binding agents neutralize SARS-CoV-2 by inhibiting binding of the spike protein to ACE2

Oscar Francesconi
Writing – Original Draft Preparation
;
Cristina Nativi
Funding Acquisition
;
Stefano Roelens
Writing – Review & Editing
2022

Abstract

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 inves- tigated 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 cytotox- icity, 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.
25
104239
104256
Oscar Francesconi, Cristina Nativi, Stefano Roelens
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2158/1268904
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