Drug repurposing screens reveal FDA approved drugs active against SARS-CoV-2
drug discovery/repurposing virology
Authors: Dittmar et al.
Link to paper: https://www.biorxiv.org/content/10.1101/2020.06.19.161042v1
Tags: Drug discovery/Drug repurpose, Virology
Vero cells have different drug sensitivity against SARS-CoV-2 from human cell lines,hence need to be used with caution in antiviral drug screening.
23 drugs against SARS-CoV-2 were discovered in human hepatocyte Huh7.5, amongst which 9 drugs are antiviral in human lung epithelial Calu-3 cells.
Cyclosporine has antiviral activity against SARS-CoV-2 through targeting Cyclophilin.
The study screened an in-house library of around 3,000 drugs in different cell types. In human hepatocyte Huh7.5 cells, 23 drugs were identified with antiviral activity and low cytotoxicity, amongst which 9 drugs were found antiviral in human lung epithelial Calu-3 cells. Cyclosporine was further investigated, providing evidence that its antiviral effect occurs through Cyclophilin, rather than Calcineurin. The authors highlighted the different susceptibility between AGM Vero cells, human hepatocyte and human lung epithelial cell lines suggesting cell-type dependent entry mechanisms for SARS-CoV-2 and emphasizing the need to be cautious when screening drugs in non-human/non-epithelial cell lines.
Impact for SARS-CoV2/COVID19 research efforts
Understand the virology and/or cell biology of SARS-CoV2/COVID19:
The findings support different receptor entry mechanisms of the virus depending on the cell type. Also, differences on cell lines permissivity to infection might point to the importance of innate sensing via RIG-I.
Treat of SARS-CoV2/COVID19 positive individuals:
The study shows an effect on human epithelial cell lines for 9 drugs, 3 of them already FDA approved.
In vitro study
Strengths and limitations of the paper
Novelty: Identified target of Cyclosporine in inhibiting SARS-CoV-2 infection in Huh7.5 and Calu-3 cells. However, drugs identified have mostly been reported to have anti-SARS-CoV-2 activity.
Standing in the field: Antiviral drugs identified agree with other studies. Suggested differences in viral entry route and drug sensitivity in different cell lines were also observed in previous literatures.
Appropriate statistics: In main figures and some supplementary figures, number of repeats and what the error bars stand for are unclear. Only outliers are shown as individual points.
Viral model used: SARS-CoV-2 [USA-WA1/2020]
Translatability:Moderately translatable. More in vitro and in vivo studies are needed for the translatability.
The study shows the effect in vitro for cell lines by virus growth on microscopy. Inhibition in cell cultures may not result in inhibition in whole organism model. The authors did not discuss whether the concentrations of drugs at which inhibition occurs have any physiological relevance. Overlapping text in the last main figure.