@article{Renz_A-2025_210956,
title = {Metabolic modeling elucidates phenformin and atpenin A5 as broad-spectrum antiviral drugs against RNA viruses},
author = {Renz, A. and Hohner, M. and Jami, R. and Breitenbach, M. and Josephs-Spaulding, J. and Dürrwald, J. and Best, L. and Dulière, V. and Mialon, C. and Marinos, G. and Leonidou, N. and Cabreiro, F. and Pellegrini, M. and Doerflinger, M. and Rosa-Calatrava, M. and Pizzorno, A. and Dräger, A. and Schindler, M. and Kaleta, C. and Bader, S.},
month = {may},
year = {2025},
abstract = {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.},
volume = {8},
journal = {Communications Biology},
publisher = {Springer Nature},
url = {https://doi.org/10.1038/s42003-025-08148-y},
}
