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models
by zope1 — last modified 2006-01-16 15:19
| By integrating all relevant available technologies covering the fields of in vitro test systems, cell culture models and in vivo animal models, VIRGIL-MODELS provides a key technological platform that allows the determination and characterization of antiviral drug resistance to complement and support the clinical platforms in combating antiviral drug resistance and to prevent the spread of drug resistant viruses by discovering the contribution of mutations to viral fitness in vitro and in vivo. Experts from the fields of biochemistry and structural biology are the main contributors to the in vitro systems. Their combined expertise creates a network that can address all aspects related to production and biochemical testing of drug resistant viral targets (e.g. polymerase, protease) as well as 3D structure determination and structure modelling in the case of drug targets for which no structure is available. Virologists and cell biologists are the main contributors to cell culture assays in VIRGIL-MODELS, which allow the testing of virus variants present in a patient sample for drug resistance in an infection or replication system. Moreover, this platform has the capabilities to generate virus mutants carrying potential drug resistance mutations and test these variants in infected cells. Finally, experts in animal models that can be used for the productive infection with HBV, HCV, and influenza combine their expertise and experimental systems in order to determine and characterize virus variants for their drug resistance in in vivo systems. |
| Although the initial focus of this platform is hepatitis viruses and influenza, the principles and integration achieved by these network relationships can be used to combat drug resistance in virtually any relevant viral disease. The integration of leading scientists capable of implementing and applying these technologies creates a unique European intellectual resource capable of tackling biochemical, virological and genomic questions related to the fundamental molecular mechanisms of the development of antiviral resistance. |
| VIRGIL-MODELS research activities are divided into three major tasks: |
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Development and implementation of genotypic and phenotypic assays to monitor drug resistance; |
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Develop and implement appropriate in vitro and cell-based assays as well as animal models to monitor and understand antiviral drug resistance; |
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Understanding at the molecular level the mechanism of antiviral drug resistance for selected viral proteins of HBV, HCV and influenza. |
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Emergence of resistance to oseltamivir among influenza A(H1N1) viruses in Europe