Metabolic Modeling Elucidates Phenformin and Atpenin A5 as Broad-Spectrum Antiviral Drugs

• DOI: 10.20944/preprints202210.0223.v2
• Publication Date: 2023-12-04T00:49:36Z
• Authors: Alina Renz; Mirjam Hohner; Maximilian Breite...; Jonathan Josephs-...; Johanna Dürrwald; Lena Best; Raphaël Jami; Georgios Marinos; Filipe Cabreiro; Andreas Dräger; Michael Schindler; Christoph Kaleta
• Keywords: Vero cell; Favipiravir; Broad spectrum; Antiviral drug

Abstract:The SARS-CoV-2 pandemic has reemphasized the urgent need for broad-spectrum antiviral therapies. We developed a computational pipeline using scRNA-Seq data to assess cellular metabolism during viral infection. With this we predicted capacity of cells sustain virion production in patients and found tissue-wide induction metabolic pathways that support replication. Expanding our analysis influenza A dengue viruses, identified targets inhibitors potential treatment. These were highly enriched known interaction partners all analyzed viruses. Indeed, phenformin, an NADH:ubiquinone oxidoreductase inhibitor, suppressed virus Atpenin A5, blocking succinate dehydrogenase, inhibited SARS-CoV-2, virus, respiratory syncytial with high selectivity indices. In vivo, phenformin showed activity against Syrian hamster model. Our work establishes host as druggable strategies, providing invaluable tools preparedness.