In general, cells carry receptors on their surface, some of which are only used for attaching viruses while others can contribute to crossing the cell barrier. Thus the S glycoprotein, present on the surface of the Coronavirus SARS-CoV-2, allows the entry of the virus into human cells via its interaction with a receptor, the ACE2 enzyme, present on the surface of infected cells. Scientists from the IBS M&P group, in collaboration with the CAID group and the IBS electron microscopy platform, as well as Spanish and Italian researchers, have demonstrated that lectin receptors (DC-SIGN, L-SIGN, MGL and Langerin) of immune cells are also able to recognize the S protein of SARS-CoV-2. This interaction involves multi-site recognition of protein S by exploiting the different glycans (sugars) on the surface of protein S. It does not cause direct infection of cells by SARS-CoV-2 but DC-SIGN and L -SIGN are able, once they have attached the virus to the cell, to transmit it to the permissive cells possessing ACE2. The S glycoprotein therefore turns out to have a whole set of keys to allow SARS-CoV-2 to proliferate.
These results, already demonstrated on pseudo viruses a few months ago in prepublication, are now confirmed by the use of authentic SARS-CoV-2 viruses, and on human respiratory cells. The researchers also demonstrated that it is possible to inhibit this mode of transmission of the virus by the use of glycomimetics, molecules that can mimic the sugars on the surfaces of the virus. These glycomimetic inhibitors developed at IBS will constitute a first tool to study, in the months to come, the relative importance of this mode of transmission. UGA press release
DC/L-SIGN recognition of spike glycoprotein promotes SARS-CoV-2 trans-infection and can be inhibited by a glycomimetic antagonist. M. Thépaut, J. Luczkowiak, C. Vivès, N. Labiod, I. Bally, F. Lasala, Y. Grimoire, D. Fenel, S. Sattin, N. Thielens, G. Schoehn, A. Bernardi, R. Delgado, F. Fieschi. Plos Pathogens (2021) accepted
– .
