Institut de Biologie StructuraleGrenoble / France

SARS-CoV-2: discovery of a new mode of transmission

Glycoprotein S, located on the SARS-CoV-2 virus membrane, is known to allow the entry of this virus into human cells via the ACE2 receptor, present on the surface of infected cells. The Membrane & Pathogens group, in collaboration with IBS/IRPAS and MEM groups and groups from Spain and Italy, have discovered that C-type lectin receptors (CLRS) of antigen-presenting cells are involved in the overall infection process. DC-SIGN, L-SIGN, Langerin and MGL bind to diverse glycans of the spike using multiple interaction areas. After attaching the virus to the cell, these lectin receptors are capable of promoting virus transfer to permissive ACE2+ cells. It is therefore a new mode of transmission in the infection process, detailed in an article posted on the BioRxiv preprint site (doi.org/10.1101/2020.08.09.242917) which is currently under evaluation by a peer-reviewed journal. They have also shown that it is possible to inhibit this new mode of virus transmission through the use of glycomimetics (sugar mimetics created by organic synthesis) previously developed at IBS.

DC/L-SIGN recognition of spike glycoprotein promotes SARS-CoV-2 trans-infection and can be inhibited by a glycomimetic antagonist. Thépaut M, Luczkowiak J, Vivès C, Labiod N, Bally I, Lasala F, Grimoire Y, Fenel D, Sattin S, Thielens N, Schoehn G, Bernardi A, Delgado R, Fieschi F. doi: https://doi.org/10.1101/2020.08.09.242917

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