Award details

Exploiting glycosylation against COVID-19

Reference	BB/V017772/1
Principal Investigator / Supervisor	Dr Alvaro Acosta-Serrano
Co-Investigators / Co-Supervisors	Dr Grant Leslie Hughes, Professor Richard Pleass
Institution	Liverpool School of Tropical Medicine
Department	Vector Biology
Funding type	Research
Value (£)	185,675
Status	Completed
Type	Research Grant
Start date	04/12/2020
End date	31/12/2022
Duration	25 months

Abstract

unavailable

Summary

In this project, we aim to expand our understanding on and exploit the essentiality of protein N-glycosylation for the control of SARS-CoV-2 transmission. N-glycosylation is the most common eukaryotic post-translational modification of proteins; it plays important roles, including protein folding and targeting as well as cell function. All SARS-CoV-2 proteins are predicted to be N-glycosylated, specially the surface homotrimeric Spike protein, which has been confirmed to have 22 N-glycans per monomer and whose structures have been recently determined. It is well known from similar coronaviruses (e.g., SARS-CoV, M-CoV) that surface glycans are important to modulate binding to the host receptor ACE2, and to reduce the accessibility of neutralising antibodies by hindering immunogenic epitopes. Although a lot of information has been obtained on the glycan structures of the Spike protein, to our knowledge, few functional studies on SARS-CoV-2 glycosylation have been performed so far. We hypothesise that interrupting the glycosylation of SARS-CoV-2 and/or host proteins will prevent viral infection and also render the virus more susceptible to the human immune system. We will do this using mainly two approaches: 1) by pharmacological inhibition of the N-glycosylation machinery and 2) by mutagenising specific N-glycan sequons on the virus Spike protein. We intend to translate the generated data into novel glycan-based therapeutics including repurposed glycosylation inhibitors to treat the disease. Our studies may also generate attenuated vaccine strains to prevent COVID-19 transmission.

Committee	Not funded via Committee
Research Topics	Microbiology
Research Priority	X – Research Priority information not available
Research Initiative	Covid19 Rapid Response [2020]
Funding Scheme	X – not Funded via a specific Funding Scheme

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