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SARS-CoV-2: a new mode of virus transmission involving immune cells

Scientists from the Institute of Structural Biology (Irig) and their partners have confirmed that the COVID-19 virus can use immune cells to increase its transmission to other cells. They also show that it is possible to inhibit this new mode of transmission of the virus through the use of glycomimetics, i.e. molecules that can mimic the surface "sugars" of the virus.

Published on 21 May 2021

On the surface of cells, certain receptors are able to "hook" onto viruses while others act as locks. Some viruses have an arsenal of proteins that allow them, like a key, to cross through the cell barrier. For example, glycoprotein S, present on the surface of SARS-CoV-2, allows the virus to enter human cells via its interaction with the ACE2 receptor, present on the surface of infected cells.

Irig scientists have discovered that the S protein also interacts with other receptors, namely proteins of the lectin family that specifically and reversibly bind to certain carbohydrates and are present on immune cells. This interaction involves multi-site recognition of the S protein at the different surface glycans (sugars) of the S protein, which would then provide a set of keys to SARS-CoV-2.

The researchers show that this interaction does not cause the direct infection of cells by SARS-CoV-2. On the contrary, some of these receptors are able to transmit the virus to cells equipped with the ACE2 receptor, once the virus has attached to the cell.

They also demonstrate that it is possible to inhibit this mode of transmission of the virus with molecules that mimic the surface sugars of the virus (glycomimetics).

The results obtained on genuine SARS-CoV-2 and on human respiratory cells confirm recent results on "pseudoviruses". Glycomimetic inhibitors will be a fundamental tool for studying the relative importance of this new mode of transmission.

This work is the result of an international collaboration involving teams from Spain (Hospital Universitario 12 de Octubre, Madrid) and Italy (Universita degli Studi di Milano).

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