VIZIER

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VIZIER “Comparative Structural Genomics of Viral Enzymes Involved in Replication” (October 2004 – October 2008)

Type of project: Integrated projectTotal EU grant: € 1.964.897

Section grant: € 373.934,00

Role: Partner

This project aimed to perform a ground-breaking impact on the identification of potential new drug targets against RNA viruses through comprehensive structural characterization of the replicative machinery of ~300 RNA viruses. RNA viruses are major human pathogens (>350 identified) causing millions of deaths annually.
The VIZIER team brought together the leading authorities on RNA viruses available in EU & more, with P4 facilities, as well as leaders in the field of structural genomics, with an adapted Management & Training structure.
VIZIER aimed to characterise RNA viruses (no DNA stage in their repl. cycle) of 3 genetically different classes: double-stranded and single stranded RNA viruses with positive & negative polarity. Their replicative machineries are the most conserved and essential viral components, thus are attractive targets for antivirus therapy. The core enzymes/proteins of the replication machinery (polymerases, helicases, capping enzymes, NTPases, proteases, ancillary replicative proteins) were characterized and compared.
One unique feature of VIZIER was the integration of major structural effort within a broad multidisciplinary study, having virology upstream and target validation (lead design) downstream. As a result, the implementation plan of the VIZIER project was structured into 5 interacting scientific sections: (i) bioinformatics, for genome annotation, target selection and data integration; (ii) virus production and genome sequencing; (iii) HTP protein production (2000-3000 targets); (iv) HTP crystallization and structural determination and (v) target validation, to assess the function of enzymes and design strategies for virus inhibition. New tools for protein production and distributed X-ray crystallography were developed and validated. This latter aspect provided a new mechanism for the fast dissemination of the gained knowledge and expertise within the European Union, inside and outside the project.