The development of vaccines and treatments to fight the SARS-CoV-2 coronavirus requires knowledge of its behavior in the body, particularly its entry points into the cells it infects. Generally speaking, cells have receptors on their surface, some of which simply act as attachment points for viruses, while others can additionally act as “locks” that viruses can manipulate for entry. To do so, viruses possess an arsenal of proteins – like a set of keys – that allows them to penetrate the cell barrier.
Glycoprotein S, present on the surface of SARS-CoV-2, allows the virus to enter human cells via its interaction with the ACE2 receptor, which is present on the surface of infected cells. Researchers at the CEA-Irig (IBS) have discovered how receptors other than ACE2 can allow the virus to infect the body. These include several receptor proteins in the lectin family (DC-SIGN, L-SIGN, MGL and Langerin) present on immune cells. “This interaction involves multi-site recognition of the S protein by exploiting the different surface glycans (sugars) of the S protein,” explains Franck Fieschi, a researcher at the CEA-Irig. Glycoprotein S thus appears to possess a full “key set” that allows SARS-CoV-2 to proliferate.
The scientists showed that this interaction does not induce the direct infection of cells by SARS-CoV-2. However, among these receptors, DC-SIGN and L-SIGN are able to transmit the virus to permissive cells expressing ACE2, once they have attached the virus to the cell. This therefore represents a new mode of transmission in the overall infection process which the researchers have presented in a publication posted on the BioRxiv preprint site, and which is currently being evaluated 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, previously developed at the Institut de Biologie Structurale (CEA-Irig). This work is the result of an international collaboration with Spanish and Italian research groups.
Interdisciplinary Research Institute of Grenoble (IRIG - CEA/CNRS/Université Grenoble Alpes)
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Instituto de Investigación Hospital Universitario 12 de Octubre (imas12), Universidad Complutense School of Medicine, Madrid
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Universita` degli Studi di Milano
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