Sökning: WFRF:(Zapatero Belinchón Francisco J.) >
Repurposing screen ...
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Haid, SibylleInstitute for Experimental Virology, Twincore - Centre for Experimental and Clinical Infection Research, Hannover, Germany
(författare)
Repurposing screen identifies novel candidates for broad-spectrum coronavirus antivirals and druggable host targets
- Artikel/kapitelEngelska2024
Förlag, utgivningsår, omfång ...
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American Society for Microbiology,2024
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electronicrdacarrier
Nummerbeteckningar
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LIBRIS-ID:oai:DiVA.org:umu-222422
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https://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-222422URI
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https://doi.org/10.1128/aac.01210-23DOI
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Språk:engelska
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Sammanfattning på:engelska
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Ämneskategori:ref swepub-contenttype
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Ämneskategori:art swepub-publicationtype
Anmärkningar
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Libraries composed of licensed drugs represent a vast repertoire of molecules modulating physiological processes in humans, providing unique opportunities for the discovery of host-targeting antivirals. We screened the Repurposing, Focused Rescue, and Accelerated Medchem (ReFRAME) repurposing library with approximately 12,000 molecules for broad-spectrum coronavirus antivirals and discovered 134 compounds inhibiting an alphacoronavirus and mapping to 58 molecular target categories. Dominant targets included the 5-hydroxytryptamine receptor, the dopamine receptor, and cyclin-dependent kinases. Gene knock-out of the drugs’ host targets including cathepsin B and L (CTSB/L; VBY-825), the aryl hydrocarbon receptor (AHR; Phortress), the farnesyl-diphosphate farnesyltransferase 1 (FDFT1; P-3622), and the kelch-like ECH-associated protein 1 (KEAP1; Omaveloxolone), significantly modulated HCoV-229E infection, providing evidence that these compounds inhibited the virus through acting on their respective host targets. Counter-screening of all 134 primary compound candidates with SARS-CoV-2 and validation in primary cells identified Phortress, an AHR activating ligand, P-3622-targeting FDFT1, and Omaveloxolone, which activates the NFE2-like bZIP transcription factor 2 (NFE2L2) by liberating it from its endogenous inhibitor KEAP1, as antiviral candidates for both an Alpha- and a Betacoronavirus. This study provides an overview of HCoV-229E repurposing candidates and reveals novel potentially druggable viral host dependency factors hijacked by diverse coronaviruses.
Ämnesord och genrebeteckningar
Biuppslag (personer, institutioner, konferenser, titlar ...)
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Matthaei, AlinaInstitute for Experimental Virology, Twincore - Centre for Experimental and Clinical Infection Research, Hannover, Germany
(författare)
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Winkler, MelinaInstitute for Experimental Virology, Twincore - Centre for Experimental and Clinical Infection Research, Hannover, Germany
(författare)
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Sake, Svenja M.Institute for Experimental Virology, Twincore - Centre for Experimental and Clinical Infection Research, Hannover, Germany
(författare)
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Gunesch, Antonia P.Institute for Experimental Virology, Twincore - Centre for Experimental and Clinical Infection Research, Hannover, Germany
(författare)
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Milke, VanessaInstitute for Experimental Virology, Twincore - Centre for Experimental and Clinical Infection Research, Hannover, Germany
(författare)
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Köhler, Natalie M.Institute for Experimental Virology, Twincore - Centre for Experimental and Clinical Infection Research, Hannover, Germany
(författare)
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Rückert, JessicaInstitute of Virology, Hannover Medical School, Hannover, Germany; German Center for Infection Research, Hannover-Braunschweig Site, Hannover, Germany
(författare)
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Vieyres, GabrielleJunior Research Group “Cell Biology of RNA Viruses”, Leibniz Institute of Experimental Virology, Hamburg, Germany; Integrative Analysis of Pathogen-Induced Compartments, Leibniz ScienceCampus InterACt, Hamburg, Germany
(författare)
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Kühl, DavidJunior Research Group “Cell Biology of RNA Viruses”, Leibniz Institute of Experimental Virology, Hamburg, Germany
(författare)
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Nguyen, Tu-TrinhCalibr, a Division, The Scripps Research Institute, La Jolla, CA, United States
(författare)
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Göhl, MatthiasGerman Center for Infection Research, Hannover-Braunschweig Site, Hannover, Germany; Helmholtz Centre for Infection Research, Braunschweig, Germany
(författare)
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Lasswitz, LisaInstitute for Experimental Virology, Twincore - Centre for Experimental and Clinical Infection Research, Hannover, Germany; Department of Biochemistry, Research Center for Emerging Infections and Zoonoses (RIZ), University of Veterinary Medicine Hannover, Hannover, Germany
(författare)
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Zapatero-Belinchón, Francisco J.Institute for Experimental Virology, Twincore - Centre for Experimental and Clinical Infection Research, Hannover, Germany; Department of Biochemistry, Research Center for Emerging Infections and Zoonoses (RIZ), University of Veterinary Medicine Hannover, Hannover, Germany
(författare)
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Brogden, GrahamInstitute for Experimental Virology, Twincore - Centre for Experimental and Clinical Infection Research, Hannover, Germany; Department of Biochemistry, Research Center for Emerging Infections and Zoonoses (RIZ), University of Veterinary Medicine Hannover, Hannover, Germany
(författare)
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Gerold, Gisa,1979-Umeå universitet,Wallenberg centrum för molekylär medicin vid Umeå universitet (WCMM),Avdelningen för virologi,Institute for Experimental Virology, Twincore - Centre for Experimental and Clinical Infection Research, Hannover, Germany; Department of Biochemistry, Research Center for Emerging Infections and Zoonoses (RIZ), University of Veterinary Medicine Hannover, Hannover, Germany; Cluster of Excellence RESIST (EXC 2155), Hannover Medical School, Hannover, Germany(Swepub:umu)gige0003
(författare)
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Wiegmann, BettinaDepartment of Cardiothoracic, Transplantation and Vascular Surgery, Hannover Medical School, Hannover, Germany; Lower Saxony Center for Biomedical Engineering, Implant Research and Development, Hannover Medical School, Hannover, Germany; BREATH (Biomedical Research in Endstage and Obstructive Lung Disease Hannover), German Center for Lung Research (DZL), Carl-Neuberg Str. 1, Hannover, Germany
(författare)
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Bilitewski, UrsulaHelmholtz Centre for Infection Research, Braunschweig, Germany
(författare)
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Brown, Richard J.P.Division of Veterinary Medicine, Paul Ehrlich Institute, Langen, Germany; Department of Molecular and Medical Virology, Ruhr University, Bochum, Germany
(författare)
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Brönstrup, MarkGerman Center for Infection Research, Hannover-Braunschweig Site, Hannover, Germany; Helmholtz Centre for Infection Research, Braunschweig, Germany
(författare)
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Schulz, Thomas F.Institute of Virology, Hannover Medical School, Hannover, Germany; German Center for Infection Research, Hannover-Braunschweig Site, Hannover, Germany; Cluster of Excellence RESIST (EXC 2155), Hannover Medical School, Hannover, Germany
(författare)
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Pietschmann, ThomasInstitute for Experimental Virology, Twincore - Centre for Experimental and Clinical Infection Research, Hannover, Germany; German Center for Infection Research, Hannover-Braunschweig Site, Hannover, Germany; Cluster of Excellence RESIST (EXC 2155), Hannover Medical School, Hannover, Germany
(författare)
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Institute for Experimental Virology, Twincore - Centre for Experimental and Clinical Infection Research, Hannover, GermanyInstitute of Virology, Hannover Medical School, Hannover, Germany; German Center for Infection Research, Hannover-Braunschweig Site, Hannover, Germany
(creator_code:org_t)
Sammanhörande titlar
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Ingår i:Antimicrobial Agents and Chemotherapy: American Society for Microbiology68:30066-48041098-6596
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- Av författaren/redakt...
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Haid, Sibylle
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Matthaei, Alina
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Winkler, Melina
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Sake, Svenja M.
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Gunesch, Antonia ...
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Milke, Vanessa
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visa fler...
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Köhler, Natalie ...
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Rückert, Jessica
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Vieyres, Gabriel ...
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Kühl, David
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Nguyen, Tu-Trinh
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Göhl, Matthias
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Lasswitz, Lisa
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Zapatero-Belinch ...
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Brogden, Graham
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Gerold, Gisa, 19 ...
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Wiegmann, Bettin ...
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Bilitewski, Ursu ...
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Brown, Richard J ...
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Brönstrup, Mark
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Schulz, Thomas F ...
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Pietschmann, Tho ...
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