Descripción del proyecto
Desarrollo de fármacos antivíricos para futuras pandemias
Los fármacos antivíricos tienen una gran importancia en la gestión de los brotes de virus. Por ello, es fundamental almacenar fármacos eficaces para cada familia de virus con potencial pandémico y tenerlos disponibles desde el primer día. En este contexto, el proyecto PANVIPREP, financiado con fondos europeos, tiene por objeto ampliar la cartera de antivíricos e identificar nuevas dianas de importancia farmacológica para virus ARN de alto riesgo. Su equipo empleará el cribado fenotípico de antivíricos, el diseño de fármacos basado en estructuras, el cribado «in silico» y métodos de aprendizaje automático para identificar entre veinticinco y cincuenta moléculas activas de gran calidad y amplio espectro. Dos de estas moléculas activas se desarrollarán hasta la fase de molécula de partida inicial, mientras que las restantes servirán como sondas químicas para identificar nuevas dianas terapéuticas en la replicación de virus ARN.
Objetivo
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.
Ámbito científico
- 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 ActionsCoordinador
2333 ZA Leiden
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