Synthetic Carbohydrate Binding Agents (CBAs) Prevent SARS-CoV-2 Entry by Inhibiting Binding of the Spike Protein to the ACE2 Receptor

Abstract

Understanding how the Severe Acute Respiratory Syndrome CoronaVirus 2 (SARS-CoV-2) highjacks epithelial cells and infiltrates organs and tissues is essential for developing strategies against this highly contagious virus. Currently, SARS-CoV-2 is thought to evade innate antiviral immunity, undergo endocytosis, and fuse with the host cell membrane by exploiting ACE2 receptors. Both, virus and ACE2, are highly glycosylated and the role of glycans in the above steps seems to be essential. Indeed, exploiting O-linked and N-linked glycans exposed on the membrane of SARS-CoV-2 as binding sites for ACE2 represents a virus strategy for infecting the human host. We unprecedentedly found that, taking advantage of small abiotic molecules capable of binding to glycans of the spike protein, binding of the latter to hACE2 can be inhibited and the viral infection can be largely neutralized. Results obtained in this work with a lead structure may open the way to the development of SARS-CoV-2 therapeutic candidates. Funding Information: Ministero dell’Universita e della Ricerca (Miur) of Italy (project n. FISR2020IP_01095). Declaration of Interests: The authors declare no competing interests.