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

Informations projet

GlycoNoVi

N° de convention de subvention: 101072717

DOI

10.3030/101072717

Date de signature de la CE 28 Juin 2022

Date de début 1 Janvier 2023

Date de fin 31 Decembre 2026

Financé au titre de

• Marie Skłodowska-Curie Actions (MSCA)

Coût total

Aucune donnée

Contribution de l’UE

€ 2 412 295,20

Coordonné par

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)

Période du rapport: 2023-01-01 au 2024-12-31

Résumé du contexte et des objectifs généraux du projet

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.

Travail effectué depuis le début du projet jusqu’à la fin de la période considérée dans le rapport et principaux résultats atteints jusqu’à présent

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.

Progrès au-delà de l’état des connaissances et impact potentiel prévu (y compris l’impact socio-économique et les conséquences sociétales plus larges du projet jusqu’à présent)

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.