Objective
G-quadruplexes (G-4) are polymorphic nucleic acid structures identified in gene promoters where they act as transcription regulators. G-4s have been found in eukaryotic and prokaryotic organisms, while very little information is available on viruses. The applicant research group has recently shown that HIV-1, which integrates into the human chromosomes and exploits cellular factors to activate transcription, takes advantage of G-4-mediated transcription regulation. G-4 disruption stimulates promoter activity while G-4 stabilization by small molecules inhibits it, showing a striking parallelism between HIV-1 LTR and eukaryotic promoter G-4s. Preliminary results indicate that similar G-4 structures form also in the viral RNA genome before retrotranscription. Available G-4 ligands, developed as anticancer drugs targeting DNA G-4, recognize both viral and cellular G-4s. Therefore, they cannot be straightforwardly used as anti-HIV compounds. The aim of this project is to develop highly specific anti-HIV-1 drugs targeting LTR DNA and/or RNA G-4s, using both reversible G-4 ligands and G-4-selective alkylating/cleaving agents, triggered by external stimuli. These approaches will be taken: a) to increase selectivity by 1) screening of ligands against LTR G-4s to select the best hits among libraries of G-4 ligands; 2) conjugation of the most promising leads to modified nucleic acids complementing LTR G-4 loop/flanking regions, to deliver the drug to its target; b) to stabilize binding by conjugation of the ligands to 3) an alkylating/cleaving subunit, and 4) an activable moiety (such as quinone methides) that alkylates the target only once the drug has reached it. Physico-chemical, biomolecular, cellular and viral assays will be used to tests the compounds. This approach should deliver reversible and irreversible ligands that selectively inhibit viral transcription and/or reverse transcription, thus preventing virus production and/or integration into the host genome.
Fields of science (EuroSciVoc)
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: The European Science Vocabulary.
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: The European Science Vocabulary.
- natural sciences biological sciences biochemistry biomolecules nucleic acids
- natural sciences biological sciences microbiology virology
- natural sciences biological sciences genetics RNA
- natural sciences biological sciences genetics genomes
- medical and health sciences basic medicine pharmacology and pharmacy pharmaceutical drugs antivirals
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Programme(s)
Multi-annual funding programmes that define the EU’s priorities for research and innovation.
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.
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
Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.
Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.
ERC-2013-CoG
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.
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.
Host institution
35122 Padova
Italy
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.