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How viruses switch between glycan and protein receptors and what it means for past and future pandemics

Project description

Uncovering how viruses cross the species barrier

Viruses enter host cells by binding to cell surface receptors through specialised glycoproteins. Some viruses, such as influenza A and coronaviruses, can switch the type of host receptor they bind to. Accumulating evidence links this transition to the emergence of viruses with pandemic potential. The ERC-funded GLYCvsPROT project aims to investigate the underlying mechanism of such receptor switching and how it affects viral infectivity and evolution. Researchers will employ structural, biochemical and biophysical methods to unveil how viral glycoproteins recognise different receptors. Overall, the work will improve monitoring of emerging pathogens and strengthen global preparedness against future pandemics.

Objective

To enter a host cell a virus needs to bind a receptor on the cell surface. Typically, viruses use specialised glycoproteins to bind to either glycans or proteins as receptors. The specificity and affinity of a virus glycoprotein for cellular receptors is a key determinant for which hosts a virus can infect. Certain enveloped viruses of high pandemic potential, such as influenza A and coronaviruses, have an ability to change their receptor specificity from a glycan to a protein receptor, and in some instances, even bind both with one glycoprotein. These receptor transitions might have contributed to emergence of pandemic viruses, such as SARS-CoV-2, and may underlie future pandemics.

Studying the structure and evolution of viral glycoproteins and their receptor complexes can help to understand the mechanisms viruses use to cross the human species barrier. I will build on my recent studies and pilot data on the structure and evolution of viral glycoproteins, and employ the glycoproteins of influenza viruses and coronaviruses which can bind to either or both receptor types to show:

- how different receptor types are recognised structurally by very similar viral glycoproteins
- how receptor type affects interaction avidity and mechanisms of viral fusion
- how receptor transitions may arise during viral evolution and influence its direction

This will be achieved by combining structural, biochemical, and biophysical approaches to reveal interactions between viral glycoproteins, influenza haemagglutinins and coronavirus spikes, with glycan and protein receptors. My studies will provide key new insights into the plasticity of viral glycoproteins and the evolutionary pathways associated with changes in receptor specificity, thus shedding light onto emergence of pandemic viruses such as SARS-CoV-2 and pandemic influenza A viruses. Importantly, this will also facilitate monitoring of emerging pathogens and increase our future pandemic preparedness.

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HORIZON-ERC - HORIZON ERC Grants

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Call for proposal

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(opens in new window) ERC-2024-STG

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Host institution

THE CHANCELLOR, MASTERS AND SCHOLARS OF THE UNIVERSITY OF OXFORD
Net EU contribution

Net EU financial contribution. The sum of money that the participant receives, deducted by the EU contribution to its linked third party. It considers the distribution of the EU financial contribution between direct beneficiaries of the project and other types of participants, like third-party participants.

€ 1 492 478,00
Address
WELLINGTON SQUARE UNIVERSITY OFFICES
OX1 2JD Oxford
United Kingdom

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Region
South East (England) Berkshire, Buckinghamshire and Oxfordshire Oxfordshire
Activity type
Higher or Secondary Education Establishments
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Total cost

The total costs incurred by this organisation to participate in the project, including direct and indirect costs. This amount is a subset of the overall project budget.

€ 1 492 478,00

Beneficiaries (1)

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