Generally, cells carry receptors on their surface, some of which are only used to bind viruses while others can act as locks that viruses use to enter. For this, they have an arsenal of proteins, like a set of switches, that allow them to cross the cell barrier. For example, the S-glycoprotein on the surface of SARS-CoV-2 allows the virus to enter human cells by interacting with ACE2 receptors on the surface of infected cells.
Interaction with proteins of the lectin family on immune cells
Scholars fromInstitute for Structural Biology (IBS) in Grenoble (CNRS / CEA / UGA), And their collaborators, they discovered that protein S also interacts, in addition to ACE2, with other receptors: the lectin family proteins (DC-SIGN, L-SIGN, MGL, and Langerin) found on immune cells. ”
This interaction involves identifying multiple sites of protein S by exploiting different glycans (polysaccharides) on the surface of the S protein. “Frank Vichy, professor at the University of Grenoble Alpes, explains. Hence, the S glycoprotein will have a whole set of keys to allow SARS-CoV-2 to proliferate.
Scientists have shown that this reaction does not cause cells to be directly infected with SARS-CoV-2. On the other hand, among these receptors, both DC-SIGN and L-SIGN are able, once the virus is attached to the cell, to transfer it to the permissible cells that possess ACE2.
Capturing of SARS-CoV2 by the DC-SIGN and / or L-SIGN receptor promotes virus-permitting transient infection (ACE2 +). Diagram on the right: The interaction between DC-SIGN or L-SIGN and a spike protein involves the identification of the glycemic “shield” (the sugars that cover the spike protein) by the sugar recognition domains of the lectin receptor. © University of Grenoble Alpes
They also explained that it is possible to prevent this pattern of virus transmission by using ice simulators, which are molecules that can simulate sugars on the surfaces of the virus.
These results, which were already demonstrated on pseudoviruses a few months ago in the pre-release stage, have now been confirmed through the use of the original SARS-CoV-2 viruses, and on human respiratory cells. Hence, the developed glycolytic inhibitors would be able to constitute the first tool to study the relative importance of this novel pattern of transmission in the coming months.