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http://dx.doi.org/10.25673/119474
Titel: | Metabolic modeling elucidates phenformin and atpenin A5 as broad-spectrum antiviral drugs against RNA viruses |
Autor(en): | Renz, Alina![]() Hohner, Mirjam Jami, Raphaël Breitenbach, Maximilian Josephs-Spaulding, Jonathan ![]() Dürrwald, Johanna Best, Lena ![]() Dulière, Victoria Mialon, Chloé Bader, Stefanie M. Marinos, Georgios Leonidou, Nantia ![]() Cabreiro, Filipe Pellegrini, Marc Doerflinger, Marcel Rosa-Calatrava, Manuel Pizzorno, Andrés Dräger, Andreas ![]() Schindler, Michael ![]() Kaleta, Christoph ![]() |
Erscheinungsdatum: | 2025 |
Art: | Artikel |
Sprache: | Englisch |
Zusammenfassung: | The SARS-CoV-2 pandemic has reemphasized the urgent need for broad-spectrum antiviral therapies. We developed a computational workflow using scRNA-Seq data to assess cellular metabolism during viral infection. With this workflow we predicted the capacity of cells to sustain SARS-CoV-2 virion production in patients and found a tissue-wide induction of metabolic pathways that support viral replication. Expanding our analysis to influenza A and dengue viruses, we identified metabolic targets and inhibitors for potential broad-spectrum antiviral treatment. These targets were highly enriched for known interaction partners of all analyzed viruses. Indeed, phenformin, an NADH:ubiquinone oxidoreductase inhibitor, suppressed SARS-CoV-2 and dengue virus replication. Atpenin A5, blocking succinate dehydrogenase, inhibited SARS-CoV-2, dengue virus, respiratory syncytial virus, and influenza A virus with high selectivity indices. In vivo, phenformin showed antiviral activity against SARS-CoV-2 in a Syrian hamster model. Our work establishes host metabolism as druggable for broad-spectrum antiviral strategies, providing invaluable tools for pandemic preparedness. |
URI: | https://opendata.uni-halle.de//handle/1981185920/121432 |
Open-Access: | ![]() |
Nutzungslizenz: | ![]() |
Journal Titel: | Communications biology |
Verlag: | Springer Nature |
Verlagsort: | London |
Band: | 8 |
Originalveröffentlichung: | 10.1038/s42003-025-08148-y |
Enthalten in den Sammlungen: | Open Access Publikationen der MLU |
Dateien zu dieser Ressource:
Datei | Größe | Format | |
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s42003-025-08148-y.pdf | 3.24 MB | Adobe PDF | Öffnen/Anzeigen |