Project description
Insight into Nidovirus replication
Nidoviruses are a varied group of RNA viruses that include well-known coronaviruses like SARS-CoV-2, as well as the lesser-studied Arteriviridae viruses, common in animal populations. The ERC-funded NidoRep project seeks to close this knowledge gap by focusing on how Arteriviridae viruses replicate, offering the first detailed look at their unique replication machinery. This study will examine how the speed and accuracy of replication differ among nidoviruses, providing crucial insights into their evolutionary diversity. By understanding these mechanisms, NidoRep aims to inform antiviral drug development targeting these diverse viruses, ultimately advancing preparedness for future viral outbreaks with epidemic potential.
Objective
Nidoviruses are an intriguing group of +RNA viruses, whose diverse genome sizes (11-41 kb) reflect a long history of adaptation to suit specific niches. They remain mostly neglected, with the exception of the large-genome Coronaviridae (CoV) family (32 kb), which includes the notorious human pathogen SARS-CoV-2. At the other end of the size-spectrum is the small-genome Arteriviridae (ArV) family (11 kb), an understudied group of prevalent, animal-infecting pathogens. Viral replication is mediated by a suite of enzymes known as the replication transcription complex (RTC), at the core of which is the RNA-dependent RNA polymerase (RdRp) and its unique Nterminal domain, known as the NiRAN. NidoRep aims to bridge the prevalent knowledge-gap between small and large genome nidoviruses, by deciphering the specific structural and mechanistic features of the RTC that regulate genome replication across such vastly different viruses. It will be divided into three distinct objectives: Objective 1 will focus on small-genome nidoviruses, providing the first structural and functional characterization of an ArV RTC. Objective 2 will probe how RdRp speed and fidelity have been fine-tuned to accommodate the distinct and conflicting replication requirements of diverse nidoviruses. This will be achieved through the development of an innovative in vitro sequencing assay, also providing a new and robust tool for screening drugs that corrupt RNA synthesis. Objective 3 will investigate the role of the NiRAN in initiation of RNA synthesis though protein-priming, providing new insight into the functional evolution of this complex domain, while also identifying novel drug-targeting sites. NidoRep will determine how specific viral enzymes have structurally and functionally evolved to support remarkable genome diversification within a single viral order. It will expand our understanding of understudied viruses with epidemic potential, and guide drug design strategies against key viral targets.
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
- medical and health sciences health sciences infectious diseases RNA viruses coronaviruses
- natural sciences biological sciences genetics RNA
- natural sciences biological sciences genetics genomes
- natural sciences biological sciences biochemistry biomolecules proteins enzymes
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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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HORIZON.1.1 - European Research Council (ERC)
MAIN PROGRAMME
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Topic(s)
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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.
HORIZON-ERC - HORIZON ERC Grants
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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) ERC-2024-STG
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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.
75794 PARIS
France
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.