Descrizione del progetto
Sviluppo di farmaci antivirali per le future pandemie
I farmaci antivirali svolgono un ruolo fondamentale nella gestione delle epidemie virali. È essenziale stoccare farmaci potenti per ogni famiglia di virus con potenziale pandemico e renderli disponibili fin dal primo giorno. In questo contesto, il progetto PANVIPREP, finanziato dall’UE, intende ampliare il portafoglio antivirale e identificare nuovi bersagli farmacologicamente rilevanti per i virus a RNA ad alto rischio. Il progetto utilizzerà lo screening fenotipico antivirale, la progettazione di farmaci basati sulla struttura, lo screening in silico e i metodi di apprendimento automatico per identificare 25-50 molecole di successo di alta qualità e ad ampio spettro. Tra questi risultati, due saranno sviluppati fino alla fase iniziale, mentre i rimanenti serviranno come composti chimici strumentali per identificare nuovi bersagli terapeutici nella replicazione dei virus a RNA.
Obiettivo
Antiviral drugs will be key in the management of future virus outbreaks. For each virus family with epidemic/pandemic potential, stockpiles of potent drugs are needed that can be deployed when a new pathogen emerges. Such broader-acting drugs (targeting conserved viral functions) are needed as of “day one” of an outbreak, for treatment and prophylaxis (e.g. in HCW and frail patients). In combination with quarantine measures, such drugs will delay (global) spread, allowing time for vaccine-development. Since the 2003 SARS outbreak, PANVIPREP’s core partners have successfully collaborated in leading European antiviral drug research projects. This provides a solid scientific basis in combination with translational drug discovery expertise. The team includes virologists, biochemists, structural biologists, medicinal chemists and pharmacokinetics experts. Previously developed know-how and toolboxes will be a major asset to achieve immediate impact. PANVIPREP aims to greatly expand the antiviral portfolio and identify novel druggable targets of high-risk RNA viruses. Hits will be identified through (i) phenotypic antiviral screening of compound libraries (ii) structure-based drug design, (iii) in silico screening, supported by the latest machine-learning methods. We will deliver 25 to 50 high-quality, broad(er)-spectrum (pan-genus/pan-family) hit molecules/hit series. Two of these will be developed to the early lead stage, including proof of concept in animal infection models. Remaining hits will serve as chemical tool-compounds to explore mechanisms of action thereby identifying novel druggable targets in RNA virus replication. This in turn will accelerate target-based drug design efforts. The workflow will integrate best practices in antiviral drug discovery with a range of methodological innovations, including AI-based methods, thus renovating and accelerating the antiviral hit discovery pipeline future use and contributing to pandemic preparedness.
Campo scientifico
- medical and health sciencesbasic medicinepharmacology and pharmacydrug discovery
- medical and health scienceshealth sciencesinfectious diseasesRNA viruses
- medical and health sciencesbasic medicinemedicinal chemistry
- medical and health scienceshealth sciencespublic healthepidemiologypandemics
- medical and health sciencesbasic medicinepharmacology and pharmacypharmaceutical drugsantivirals
Parole chiave
Programma(i)
Meccanismo di finanziamento
HORIZON-RIA - HORIZON Research and Innovation ActionsCoordinatore
2333 ZA Leiden
Paesi Bassi