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Content archived on 2024-05-30

Small Molecule Inhibitors of the Trimeric Influenza Virus Polymerase Complex

Objective

The clock is counting down to the next influenza pandemic. Since 1997, the avian influenza virus strain H5N1 has infected over 250 people worldwide with a fatality rate of ~60%, although so far without sustained human-to-human transmission. In view of the very few efficacious drugs against influenza virus infections and the time it takes to develop a matching vaccine, there is an unmet worldwide need for new anti-influenza drugs. The viral trimeric RNA polymerase complex, consisting of the subunits PA, PB1 and PB2, is an attractive target for inhibition of viral replication. However, due to the absence of detailed structural information and clear understanding of the subunit functions so far, inhibitors of the RNA polymerase developed as drug candidates are extremely scarce. Based on the recent finding that a short peptide corresponding to the PA-binding domain of the PB1 subunit blocks both polymerase activity and viral spread, FLUINHIBIT aims at discovering small molecule inhibitors of this subunit interaction crucial for viral replication. Starting from the peptide, and supported by characterization of the PB1-binding domain of PA, molecular modeling will be employed to rationally design and synthesize peptidomimetics via traditional medicinal chemistry and a novel fragment based library synthesis approach. In parallel, a fluorescence polarization high-throughput assay will be developed to screen large compound collections and unique in-house small molecule libraries. The resulting hits will be profiled in cell-based assays and lead candidates with antiviral activity will be identified for preclinical development.

Fields of science (EuroSciVoc)

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Keywords

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Programme(s)

Multi-annual funding programmes that define the EU’s priorities for research and innovation.

Topic(s)

Calls for proposals are divided into topics. A topic defines a specific subject or area for which applicants can submit proposals. The description of a topic comprises its specific scope and the expected impact of the funded project.

Call for proposal

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FP7-HEALTH-2007-A
See other projects for this call

Funding Scheme

Funding scheme (or “Type of Action”) inside a programme with common features. It specifies: the scope of what is funded; the reimbursement rate; specific evaluation criteria to qualify for funding; and the use of simplified forms of costs like lump sums.

CP-FP - Small or medium-scale focused research project

Coordinator

PIKE PHARMA GMBH
EU contribution
€ 378 750,00
Address
TECHNOPARKSTRASSE 1
CH-8005 ZUERICH
Switzerland

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Activity type
Private for-profit entities (excluding Higher or Secondary Education Establishments)
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Total cost

The total costs incurred by this organisation to participate in the project, including direct and indirect costs. This amount is a subset of the overall project budget.

No data

Participants (5)

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