Classical drug digitoxin inhibits influenza cytokine storm, with implications for COVID-19 therapy
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Abstract
Influenza viruses, corona viruses and related pneumotropic viruses cause sickness and death partly by inducing a hyper-proinflammatory response by immune cells and cytokines in the host airway. Here we show that the cardiac glycoside digitoxin suppresses this response induced by influenza virus strain A/Wuhan/H3N2/359/95 in the cotton rat lung. The cytokines TNFα, GRO/KC, MIP2, MCP1, TGFβ, and IFNγ. are significantly and differentially reduced. Since the hyper-proinflammatory expression of cytokines is a host response, we suggest that digitoxin may have therapeutic potential for not only influenza and but also for coronavirus infections.
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SciScore for 10.1101/2020.04.09.034983: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Institutional Review Board Statement IACUC: All experiments were performed using protocols that followed federal guidelines and were approved by the Institutional Animal Care and Use Committee. Randomization not detected. Blinding not detected. Power Analysis not detected. Sex as a biological variable not detected. Table 2: Resources
No key resources detected.
Results from OddPub: We did not detect open data. We also did not detect open code. Researchers are encouraged to share open data when possible (see Nature blog).
Results from LimitationRecognizer: We detected the following sentences addressing limitations in the study:Finally, since antiviral properties have been reported for digitoxin and other cardiac …
SciScore for 10.1101/2020.04.09.034983: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Institutional Review Board Statement IACUC: All experiments were performed using protocols that followed federal guidelines and were approved by the Institutional Animal Care and Use Committee. Randomization not detected. Blinding not detected. Power Analysis not detected. Sex as a biological variable not detected. Table 2: Resources
No key resources detected.
Results from OddPub: We did not detect open data. We also did not detect open code. Researchers are encouraged to share open data when possible (see Nature blog).
Results from LimitationRecognizer: We detected the following sentences addressing limitations in the study:Finally, since antiviral properties have been reported for digitoxin and other cardiac glycosides, it is a limitation of the study that we cannot exclude other antiviral effects by digitoxin from contributing to the reduction in influenza-dependent cytokine concentrations (Burkard et al., 2015; Amarelle and Lecuona, 2018; Wei et al., 2020). In conclusion, these data show that digitoxin blocks the host cytokine storm induced by influenza strain A/Wuhan/H3N2/359/95 in the cotton rat lung. Since digitoxin already had been shown to be safe in CF patients with pulmonary disease and a normal heart, and caused a similar reduction in NF-KB driven cytokine expression, this drug may be a good candidate for further investigation as a therapy for influenza and potentially for COVID-19.
Results from TrialIdentifier: No clinical trial numbers were referenced.
Results from Barzooka: We did not find any issues relating to the usage of bar graphs.
Results from JetFighter: We did not find any issues relating to colormaps.
Results from rtransparent:- Thank you for including a conflict of interest statement. Authors are encouraged to include this statement when submitting to a journal.
- No funding statement was detected.
- No protocol registration statement was detected.
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