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

Alina Renz; Mirjam Hohner; Maximilian Breitenbach; Jonathan Josephs-Spaulding; Johanna Dürrwald; Lena Best; Raphaël Jami; Georgios Marinos; Filipe Cabreiro; Andreas Dräger; Michael Schindler; Christoph Kaleta

doi:10.20944/preprints202210.0223.v1

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preprints.org > biology and life sciences > virology > doi: 10.20944/preprints202210.0223.v1

Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

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

Alina Renz

Mirjam Hohner

Maximilian Breitenbach

Jonathan Josephs-Spaulding

^* ,

^* ,

Version 1 : Received: 14 October 2022 / Approved: 17 October 2022 / Online: 17 October 2022 (03:42:37 CEST)
Version 2 : Received: 30 November 2023 / Approved: 30 November 2023 / Online: 30 November 2023 (16:08:09 CET)
Version 3 : Received: 22 March 2024 / Approved: 22 March 2024 / Online: 22 March 2024 (16:46:59 CET)

How to cite: Renz, A.; Hohner, M.; Breitenbach, M.; Josephs-Spaulding, J.; Dürrwald, J.; Best, L.; Jami, R.; Marinos, G.; Cabreiro, F.; Dräger, A.; Schindler, M.; Kaleta, C. Metabolic Modeling Elucidates Phenformin and Atpenin A5 as Broad-Spectrum Antiviral Drugs. Preprints 2022, 2022100223. https://doi.org/10.20944/preprints202210.0223.v1 Renz, A.; Hohner, M.; Breitenbach, M.; Josephs-Spaulding, J.; Dürrwald, J.; Best, L.; Jami, R.; Marinos, G.; Cabreiro, F.; Dräger, A.; Schindler, M.; Kaleta, C. Metabolic Modeling Elucidates Phenformin and Atpenin A5 as Broad-Spectrum Antiviral Drugs. Preprints 2022, 2022100223. https://doi.org/10.20944/preprints202210.0223.v1

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MDPI and ACS Style

Renz, A.; Hohner, M.; Breitenbach, M.; Josephs-Spaulding, J.; Dürrwald, J.; Best, L.; Jami, R.; Marinos, G.; Cabreiro, F.; Dräger, A.; Schindler, M.; Kaleta, C. Metabolic Modeling Elucidates Phenformin and Atpenin A5 as Broad-Spectrum Antiviral Drugs. Preprints 2022, 2022100223. https://doi.org/10.20944/preprints202210.0223.v1

APA Style

Renz, A., Hohner, M., Breitenbach, M., Josephs-Spaulding, J., Dürrwald, J., Best, L., Jami, R., Marinos, G., Cabreiro, F., Dräger, A., Schindler, M., & Kaleta, C. (2022). Metabolic Modeling Elucidates Phenformin and Atpenin A5 as Broad-Spectrum Antiviral Drugs. Preprints. https://doi.org/10.20944/preprints202210.0223.v1

Chicago/Turabian Style

Renz, A., Michael Schindler and Christoph Kaleta. 2022 "Metabolic Modeling Elucidates Phenformin and Atpenin A5 as Broad-Spectrum Antiviral Drugs" Preprints. https://doi.org/10.20944/preprints202210.0223.v1

Abstract

The SARS-CoV-2 pandemic has reemphasized the urgent need to develop broad-spectrum antiviral therapies. Wedeveloped a computational pipeline that uses scRNA-Seq data to reconstruct the metabolic state of cells and tissuesduring viral infection. Using this pipeline, we investigated the cellular capacity to produce SARS-CoV-2 virions invarious tissues and disease conditions. Subsequently, we expanded our analysis to influenza A and dengue virus andidentified several metabolic targets and their inhibitors for broad-spectrum antiviral treatment. Phenformin, an inhibitorof NADH:ubiquinone oxidoreductase, suppressed SARS-CoV-2 and dengue virus replication. Using Atpenin A5 toblock the succinate dehydrogenase inhibited SARS-CoV-2, dengue virus, influenza A virus and respiratory syncytialvirus with superior therapeutic indices. Thus, our work establishes host metabolism as druggable for broad antiviraltherapy. Moreover, our pipeline, the identified targets, and inhibitors are invaluable tools for pandemic preparedness.

Supplementary and Associated Material

https://github.com/draeger-lab/R-DRUGS: GitHub repository of scripts and analyses

Keywords

Drug discovery; Systems biology; SARS-CoV-2; Dengue; Influenza A; RSV; cell viability analysis; antivirals

Subject

Biology and Life Sciences, Virology

Copyright: This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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