Submitted:
14 October 2022
Posted:
17 October 2022
Read the latest preprint version here
Preprints on COVID-19 and SARS-CoV-2
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.
Keywords:
Drug discovery
; Systems biology
; SARS-CoV-2
; Dengue
; Influenza A
; RSV
; cell viability analysis
; antivirals
Copyright: This open access article is published under a Creative Commons CC BY 4.0 license, which permit the free download, distribution, and reuse, provided that the author and preprint are cited in any reuse.
