Institut de Biologie StructuraleGrenoble / France

SARS-CoV-2 : a new mode of transmission

Broadly speaking, cells have receptors on their surface, some of which are used only for virus attachment, while others can contribute to the cellular barrier crossing. The S-glycoprotein, located on the surface of the SARS-CoV-2 Coronavirus, allows the entry of the virus into human cells via its interaction with a receptor, the ACE2 enzyme, on the surface of infected cells.
IBS Scientists (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 a multi-site recognition of the S protein by exploiting the different surface glycans (sugars) of the S protein. 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 permissive cells possessing ACE2. The S-glycoprotein thus appears to possess a whole set of keys to allow SARS-CoV-2 to proliferate.
These results, already demonstrated on pseudo viruses a few months ago in pre-publication, are now confirmed by the use of authentic SARS-CoV-2 viruses and on human respiratory cells. The researchers have also demonstrated that it is possible to inhibit this mode of transmission by using glycomimetics, molecules that can mimic the surface sugars of the virus. These glycomimetic inhibitors developed at IBS will constitute a first tool to study 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) accepté

Contact : Franck Fieschi, UGA professor attached to the IBS (Membrane & Pathogens group)