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Antivirus Pandemic Preparedness EuropeAn pLatform

Project description

Antiviral drug against potential emerging and re-emerging viruses

Developing new antiviral treatments against viruses is crucial, particularly for those identified by the WHO as high-priority emerging and re-emerging viruses. Broad-spectrum host-directed antiviral drugs (HDA) present a promising option for treatment. However, identifying relevant host factors through genome-wide knockout screens poses challenges due to inconsistencies in the resulting hits. The EU-funded APPEAL project aims to establish a pipeline for identifying and validating antivirals for specific viruses and discovering at least one broad-spectrum antiviral drug against potential emerging and re-emerging viruses listed by the WHO. The pipeline will use machine learning, High-Density Cell Arrays, and gene descriptors to identify host restriction factors that impede the virus.

Objective

Developing new antiviral treatment against viruses and particularly high-priority emerging and re-emerging viruses as listed by the WHO, remains crucial as, among other aspects, the viruses evolve under selection. Broad spectrum host-directed antiviral drugs (HDA) are promising therapeutic options, however the robust identification of relevant host factors by genome-wide knockout screens is challenging due to low consistency in the resulting hits. Our project aims to (1) establish a computational and experimental pipeline to identify and validate an antiviral for these viruses, and (2) identify at least one broad spectrum antiviral drug against potential emerging and re-emerging viruses as listed by the WHO. To address these, we will implement a drug selection pipeline following several strategies: We will employ (i) machine learning, based on data from knockout screens, proteomics, protein interaction, transcriptomics of infected cells with pandemic-related viruses, Genome-Wide Association Studies, and generic gene descriptors, (ii) High Density Cell Arrays, which provide much more detailed readouts compared to state of the art pooled knockout screens, (iii) primary cell cultures obtained from a diverse array of human tissues, as they are more appropriate to study the host cell physiology during infection, compared to cancer cell lines, and (iv) use the pipeline to identify host restriction factors, which, when activated, challenge the virus; followed by innovative drug development and delivery based on small activating RNA. The pipeline comprises an Expedited Arm for which broad spectrum antiviral drugs for repurposing will be selected followed by in vitro and in vivo efficacy testing, and a clinical trial as a proof of concept. The elaborated Arm includes all strategies (i)-(iv) and will provide a sustainable pandemic preparedness pipeline ready-to-operate to identify the appropriate treatment against the emerging virus at the early time of a new outbreak.

Fields of science (EuroSciVoc)

Keywords

Programme(s)

Topic(s)

Funding Scheme

HORIZON-RIA - HORIZON Research and Innovation Actions

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Call for proposal

(opens in new window) HORIZON-HLTH-2023-DISEASE-03

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Coordinator

UNIVERSITATSKLINIKUM JENA
Net EU contribution
€ 1 714 516,25
Address
KASTANIENSTR.1
07747 Jena
Germany
Region
Thüringen Thüringen Jena, Kreisfreie Stadt
Activity type
Higher or Secondary Education Establishments
Links
Total cost
€ 1 714 516,25

Participants (13)

Partners (1)