Understanding the Role of Glycans in Human Norovirus Infection: a Key to Unlock New Therapies

Projektinformationen

GlycoNoVi

ID Finanzhilfevereinbarung: 101072717

DOI

10.3030/101072717

EK-Unterschriftsdatum 28 Juni 2022

Startdatum 1 Januar 2023

Enddatum 31 Dezember 2026

Finanziert unter

• Marie Skłodowska-Curie Actions (MSCA)

Gesamtkosten

Keine Daten

EU-Beitrag

€ 2 412 295,20

Koordiniert durch

UNIVERSITA DEGLI STUDI DI FIRENZE
Italy

Periodic Reporting for period 1 - GlycoNoVi (Understanding the Role of Glycans in Human Norovirus Infection: a Key to Unlock New Therapies)

Berichtszeitraum: 2023-01-01 bis 2024-12-31

Zusammenfassung vom Kontext und den Gesamtzielen des Projekts

Norovirus infections are a major global health concern, causing acute gastroenteritis outbreaks with significant socio-economic impact. The GlycoNoVi project aims to unravel the role of glycans in norovirus infections, paving the way for novel antiviral strategies. By combining synthetic chemistry, structural biology, and virology, the project seeks to develop glycan-based therapeutics and diagnostics, ultimately reducing the burden of norovirus-related diseases worldwide.

Arbeit, die ab Beginn des Projekts bis zum Ende des durch den Bericht erfassten Berichtszeitraums geleistet wurde, und die wichtigsten bis dahin erzielten Ergebnisse

During the first reporting period, GlycoNoVi made significant progresses in understanding norovirus-glycan interactions. Key norovirus strains were identified, and recombinant VP1 proteins were successfully expressed in both bacterial and mammalian systems for structural and functional studies. Synthetic and enzymatic methods have been succesfully accomplished and the new compounds prepared enabled the implementation of already available glycan libraries. Currently new compounds and compounds part of the library are under screening for their binding properties and antiviral potential. Structural characterization of newly expressed viral proteins and of protein-small molecules binding have been performed or are in progress.
The NMR and molecular dynamics data obtained provided intresting insights into glycan-protein recognition and interaction. Additionally, novel approaches, such as the development of fucose-enriched biopolymers and covalent inhibitors, are under development.
Scientific activities and partners interactions are in line with the original plan.

Fortschritte, die über den aktuellen Stand der Technik hinausgehen und voraussichtliche potenzielle Auswirkungen (einschließlich der bis dato erzielten sozioökonomischen Auswirkungen und weiter gefassten gesellschaftlichen Auswirkungen des Projekts)

GlycoNoVi is advancing the understanding of norovirus-glycan interactions through innovative approaches that go beyond the current state of the art. The project has developed a unique library of synthetic and enzymatically produced glycans, enabling high-precision screening for antiviral properties. Cutting-edge structural techniques, including advanced NMR and molecular modeling, have provided intresting insight into glycan binding mechanisms. Additionally, novel covalent inhibitors and multivalent glycan constructs are being explored as potential therapeutic strategies.
A panel of norovirus strains was cloned and recombinant proteins were cloned to generate VLPs, VP1-luciferease and P domains.
Small crystals clusters were obtained for GII.17 P domain, a genotype considered to be an emergent and circulating strain. Co-crystallisation of HMOs and blood group antigens with GII.17 P domain is under optimization.
These findings might greatly contribute to the design of new antiviral approaches, the development of innovative diagnostic tools and to future clinical translation. To maximize the impact of the project, in addition to the network’s industrial partners, regulatory support, and collaborations with actors outside the consortium are taken into account.