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AI-driven discovery broad-spectrum antivirals targeting Nucleocytoviricota factories via phase separation modulation

Project description

Designing antivirals with the help of AI

Nucleocytoviricota viruses, including monkeypox virus and African swine fever virus, are large DNA viruses that pose serious public health issues. These viruses replicate within specialised membrane-less organelles, known as viral factories, which depend on conserved scaffold proteins. Considering the lack of antivirals, the ERC-funded PSDisrupt project proposes to design small molecules that disrupt viral factory formation and inhibit virus replication. Researchers will employ AI to screen large chemical spaces to identify both broad-spectrum and virus-specific inhibitors. Following validation at the biophysical and cellular levels, promising compounds will be brought forward for preclinical development and pharmaceutical partnerships.

Objective

"The phylum Nucleocytoviricota includes (re-)emerging dsDNA viruses of major concern, such as monkeypox virus (mpox) and African swine fever virus (ASFV). Despite their economic and public health impact, no formally approved antivirals exist for these pathogens. Viral factories (membrane-less organelles essential for replication) are highly conserved across Nucleocytoviricota, presenting an attractive and untapped target for antiviral intervention.
PSDisrupt builds on findings from the ERC-funded ViDaMa project, which identified scaffold proteins governing phase separation in viral factories. These proteins share a conserved ""molecular grammar"" essential for condensate formation. Disrupting this process is expected to broadly inhibit viral replication while minimizing the development of resistance.
This PoC project will design phase-separation grammar-targeting antivirals using AI-driven pipelines. Deep learning models will enable the screening of ultra-large chemical spaces to identify: (i) broad-spectrum inhibitors targeting conserved scaffold proteins across Nucleocytoviricota, and/or (ii) virus-specific antivirals for mpox and ASFV.
PSDisrupt’s translational goal is to design and advance lead compounds into preclinical validation and assess their commercial potential. We will:
- Discover and design drugs by leveraging high throughput screens and deep learning-based algorithms.
- Perform biophysical and cellular assays to validate compound efficacy.
- Establish IP protection for novel inhibitors.
- Engage with pharmaceutical and biotech partners for licensing and further development.
By bridging virology and AI-driven drug design, PSDisrupt pioneers a novel antiviral strategy with broad applications beyond infectious diseases. The AI framework could be adapted to target phase separation in diverse pathological conditions, including cancer, neurodegeneration, and other condensate-associated diseases, significantly expanding its biomedical and commercial impact.
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HORIZON-ERC-POC - HORIZON ERC Proof of Concept Grants

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(opens in new window) ERC-2025-POC

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Host institution

CENTRE NATIONAL DE LA RECHERCHE SCIENTIFIQUE CNRS
Net EU contribution

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.

€ 150 000,00
Address
RUE MICHEL ANGE 3
75794 PARIS
France

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Region
Ile-de-France Ile-de-France Paris
Activity type
Research Organisations
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