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CORDIS

Antivirus Pandemic Preparedness EuropeAn pLatform

Descrizione del progetto

Farmaco antivirale contro potenziali virus emergenti e riemergenti

Lo sviluppo di nuovi trattamenti antivirali contro i virus è fondamentale, in particolare per quelli identificati dall’OMS come virus emergenti e riemergenti ad alta priorità. I farmaci antivirali ad ampio spettro diretti dall’ospite (HDA) rappresentano un’opzione promettente per il trattamento. Tuttavia, l’identificazione di fattori ospiti rilevanti attraverso screening knockout a livello genomico pone delle sfide a causa delle incongruenze nei risultati ottenuti. Il progetto APPEAL, finanziato dall’UE, intende creare una pipeline per l’identificazione e la validazione di antivirali per virus specifici e a scoprire almeno un farmaco antivirale ad ampio spettro contro i potenziali virus emergenti e riemergenti elencati dall’OMS. La pipeline utilizzerà l’apprendimento automatico, gli array cellulari ad alta densità e i descrittori genici per identificare i fattori di restrizione dell’ospite che ostacolano il virus.

Obiettivo

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.

Campo scientifico (EuroSciVoc)

Parole chiave

Programma(i)

Argomento(i)

Meccanismo di finanziamento

HORIZON-RIA - HORIZON Research and Innovation Actions

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Invito a presentare proposte

(si apre in una nuova finestra) HORIZON-HLTH-2023-DISEASE-03

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Coordinatore

UNIVERSITATSKLINIKUM JENA
Contributo netto dell'UE
€ 1 714 516,25
Indirizzo
KASTANIENSTR.1
07747 Jena
Germania
Regione
Thüringen Thüringen Jena, Kreisfreie Stadt
Tipo di attività
Higher or Secondary Education Establishments
Collegamenti
Costo totale
€ 1 714 516,25

Partecipanti (13)

Partner (1)