The VIZIER project: overview; expectations; and achievements

Abstract

VIZIER is an acronym for a research project entitled "Comparative Structural Genomics of Viral Enzymes Involved in Replication" funded by the European Commission between November 1st, 2004 and April 30th, 2009. It involved 25 partners from 12 countries. In this paper, we describe the organization of the project and the culture created by its multidisciplinary essence. We discuss the main thematic sections of the project and the strategy adopted to optimize the integration of various scientific fields into a common objective: to obtain crystal structures of the widest variety of RNA virus replication enzymes documented and validated as potential drug targets. We discuss the thematic sections and their overall organization, their successes and bottlenecks around the protein production pipeline, the "low hanging fruit" strategy, and measures directed to problem solving. We discuss possible future options for such large-scale projects in the area of antiviral drug design. In a series of accompanying papers in Antiviral Research, the project and its achievements are presented for each virus family.

Fig. 1

The status of viral targets through the VIZIER production pipeline. The steps represent the advancement of targets under the form of in silico sequences (submitted), cDNA derived from viral RNA (PCR and cloned), recombinant protein expressed under a soluble form (soluble), purified, submitted to crystallogenesis (Xtal screen), and whose crystal structure has been determined (structure). Unique structure refers to a crystal structure of a single protein, either in complex or unliganded. Blue stacks represent the actual achievements compared to the objectives of the project (red stacks) . (For interpretation of the references to color in the citation of this figure, the reader is referred to the web version of the article.)