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Identification of viroporin blockers for future antiviral therapy using automated high-throughput screening

Project description

Novel antivirals for future outbreaks

The life cycle of RNA viruses involves viral replication and release from host cells through the membrane using specific proteins known as viroporins. Although viroporin blockers have shown therapeutic potential, their clinical success has been limited by resistance and low potency. The ERC-funded ViPoFluX project aims to develop novel antivirals that target viroporins, hoping to address the threat of future viral pandemics. Researchers will undertake a high-throughput screening process using a novel viroporin inhibitor assay to test over 50 000 compounds. The process will include target identification and cross-validation to identify potential lead compounds for further exploitation.

Objective

The potential for future viral pandemics to trigger a global crisis underscores the urgent need for the development of new antiviral drugs. Viroporins, identified in several RNA virus families, form pores/ion channels in cell and/or virus membranes, contributing to the virus life cycle and virus-induced pathology. Blocking viroporins with small-molecule compounds has proven to be an effective therapeutic strategy. However, the clinical success of these viroporin blockers has been limited due to emerging resistance and insufficient potency when repurposed for other viroporin targets. Expanding the repository of viroporin blockers by identifying new compounds that potently inhibit virus infections will advance the pandemic preparedness and likely make drug repurposing more successful in the future. A major challenge is the current methodology for exploring viroporin blockers, which is traditionally time-consuming and has low throughput. In this project. we will combine our novel viroporin inhibitor assay with an automated high-throughput screening (HTS) platform and a library of 50,000 compounds, creating a pipeline suitable for identifying new blockers of potentially any given viroporin. Our pipeline consists of four steps: (I) the identification of viroporin targets, (II) HTS, (III) cross-validation and (IV) and hit-to-lead optimization. Preliminary data from our group demonstrates the feasibility of the assay for viroporins from viruses relevant to global health. We plan to screen relevant viroporins in HTS to develop novel, high potency viroporin inhibitors and file intellectual property (IP) for rationally optimized hit compounds. Once the IP is filed, we will establish a spin-out company to raise funds from public and private sources, advancing our proof-of-concept studies and developing the lead compound further.

Programme(s)

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Topic(s)

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Funding Scheme

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HORIZON-ERC-POC - HORIZON ERC Proof of Concept Grants

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Call for proposal

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(opens in new window) ERC-2024-POC

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Host institution

KOBENHAVNS UNIVERSITET
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
NORREGADE 10
1165 KOBENHAVN
Denmark

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Region
Danmark Hovedstaden Byen København
Activity type
Higher or Secondary Education Establishments
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Total cost

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No data

Beneficiaries (1)

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