Project description
Molecular inhibition of viral infectivity
Viruses must hijack cellular machinery to survive, replicate and spread. To maximise the information content of their genomes, viruses have adopted the mechanism of programmed ribosomal frameshifting, which allows parallel translation of multiple protein copies from the same mRNA molecule. The EU-funded RIBOSFL project focuses on the restriction factor Shiftless (SFL), which is known to block virus infectivity by inhibiting ribosomal frameshifting. Researchers aim to study the mechanism of action of SFL, which will pave the way for the design of new antiviral therapeutics. This is of great clinical significance for key pathogens such as HIV and SARS-CoV-2.
Objective
Programmed ribosomal frameshifting (PRF) is a mechanism of recoding that allows synthesis of multiple proteins from the same mRNA by shifting the translation reading frame. Many viruses, including medically important HIV and coronaviruses rely on PRF to increase their coding capacity and modulate appropriate stoichiometric ratios of viral proteins. An interferon-inducible restriction factor Shiftless (SFL) can block the frameshifting required for viral translation and infectivity. Understanding the mechanism of action of SFL will undoubtedly guide the design of new antiviral therapeutics. However, most structural and functional aspects of SFL and its role in viral infections are unknown. We intend to characterise the role of SFL in HIV and coronavirus infections using a three-pronged approach: (i) We will elucidate the mechanism of inhibition of PRF on viral mRNAs by SFL using a state-of-the-art in vitro reconstituted translation system and depletion/deletion of SFL in human cell lines. (ii) We will determine the interaction of SFL, translating ribosome and frameshifting viral mRNAs using cryo-electron microscopy. (iii) Based on the structural data obtained, we will generate mutants of SFL and characterise their activities by in vitro and cellular translation assays to identify specific domains and amino acid residues required for the antiviral activity of SFL. The results expected from our proposed study should not only be crucial for understanding the molecular mechanism of SFL but should also provide vital inputs to the development of antiviral therapeutic agents by either mimicking or upregulating SFL expression against critically important viruses such as HIV and SARS-CoV-2. Importantly, our research should continue to be relevant for the treatment of any future frameshifting virus.
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 microbiology virology
- natural sciences biological sciences biochemistry biomolecules proteins
- medical and health sciences health sciences infectious diseases RNA viruses HIV
- medical and health sciences health sciences infectious diseases RNA viruses coronaviruses
- natural sciences chemical sciences organic chemistry amines
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Keywords
Project’s keywords as indicated by the project coordinator. Not to be confused with the EuroSciVoc taxonomy (Fields of science)
Project’s keywords as indicated by the project coordinator. Not to be confused with the EuroSciVoc taxonomy (Fields of science)
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.
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H2020-EU.1.3. - EXCELLENT SCIENCE - Marie Skłodowska-Curie Actions
MAIN PROGRAMME
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H2020-EU.1.3.2. - Nurturing excellence by means of cross-border and cross-sector mobility
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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.
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.
MSCA-IF - Marie Skłodowska-Curie Individual Fellowships (IF)
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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.
(opens in new window) H2020-MSCA-IF-2020
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Net EU financial contribution. The sum of money that the participant receives, deducted by the EU contribution to its linked third party. It considers the distribution of the EU financial contribution between direct beneficiaries of the project and other types of participants, like third-party participants.
80539 MUNCHEN
Germany
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.