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Comparative structural genomics of viral enzymes involved in replication


This project aims to perform a ground-breaking impact on the identification of potential new drug targets against RNA viruses through comprehensive structural characterisation of the replicative machinery of -300 RNA viruses. RNA viruses are major human pa thogens (>350 identified) causing millions of deaths annually. The VIZIER team brings 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 aims 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 m achineries 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) will be characterised and compared. One unique feature of VIZIER is the integration of major structural effort within a broad multidisciplinary study, having virology upstream and target validation (lead design) downstream. As a result, the imple mentation plan of the VIZIER project is 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 (2000-300 0 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 will be develo ped and validated. This latter aspect will provide a new mechanism for the fast dissemination of the gained knowledge and expertise within the European Union, inside and outside the #

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58 bd charles livon, jardin du pharo

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Participants (25)