Projektbeschreibung
Antivirale Wirkstoffe für zukünftige Pandemien entwickeln
Antivirale Wirkstoffe spielen bei der Bekämpfung von Virenausbrüchen eine Hauptrolle. Von entscheidender Bedeutung ist, für jede Virusfamilie mit Pandemiepotenzial wirksame Arzneimittel vorrätig zu halten und sie vom ersten Tag an zur Verfügung zu stellen. In diesem Zusammenhang lautet das Ziel des EU-finanzierten Projekts PANVIPREP, das antivirale Portfolio zu erweitern und neue pharmakologisch relevante Ziele für Hochrisiko-RNS-Viren zu ermitteln. Im Rahmen des Projekts werden phänotypisches antivirales Screening, strukturbasiertes Wirkstoffdesign, In-silico-Screening und Methoden des maschinellen Lernens eingesetzt, um 25 bis 50 hochwertige Hit-Moleküle mit breitem Wirkungsspektrum zu identifizieren. Von diesen Treffern werden zwei bis zum Frühstadium der Leitstruktur entwickelt, während die übrigen Treffer als chemische Hilfsverbindungen zur Erkennung neuartiger therapeutischer Ziele bei der RNS-Virusreplikation dienen werden.
Ziel
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.
Wissenschaftliches Gebiet
- 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
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HORIZON-RIA - HORIZON Research and Innovation ActionsKoordinator
2333 ZA Leiden
Niederlande