SGLT2‐Inhibition reverts urinary peptide changes associated with severe COVID‐19: An in‐silico proof‐of‐principle of proteomics‐based drug repurposing
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Abstract
Severe COVID‐19 is reflected by significant changes in urine peptides. Based on this observation, a clinical test predicting COVID‐19 severity, CoV50, was developed and registered as in vitro diagnostic in Germany. We have hypothesized that molecular changes displayed by CoV50, likely reflective of endothelial damage, may be reversed by specific drugs. Such an impact by a drug could indicate potential benefits in the context of COVID‐19. To test this hypothesis, urinary peptide data from patients without COVID‐19 prior to and after drug treatment were collected from the human urinary proteome database. The drugs chosen were selected based on availability of sufficient number of participants in the dataset ( n > 20) and potential value of drug therapies in the treatment of COVID‐19 based on reports in the literature. In these participants without COVID‐19, spironolactone did not demonstrate a significant impact on CoV50 scoring. Empagliflozin treatment resulted in a significant change in CoV50 scoring, indicative of a potential therapeutic benefit. The study serves as a proof‐of‐principle for a drug repurposing approach based on human urinary peptide signatures. The results support the initiation of a randomized control trial testing a potential positive effect of empagliflozin for severe COVID‐19, possibly via endothelial protective mechanisms.
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SciScore for 10.1101/2021.07.21.21260351: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Ethics IRB: All underlying studies were conducted to conform to regulations on the protection of individuals participating in medical research and in accordance with the principles of the Declaration of Helsinki (2013) and received ethical approval by the responsible institutional review boards.
Consent: Written informed consent was obtained from all participants at the time of sampling.Sex as a biological variable not detected. Randomization All samples from subjects undergoing spironolactone treatment and placebo controls were from the HOMAGE trial, a prospective, randomized, open-label, blinded-endpoint (PROBE), multicentre design, in which people at increased risk of developing HF were randomly … SciScore for 10.1101/2021.07.21.21260351: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Ethics IRB: All underlying studies were conducted to conform to regulations on the protection of individuals participating in medical research and in accordance with the principles of the Declaration of Helsinki (2013) and received ethical approval by the responsible institutional review boards.
Consent: Written informed consent was obtained from all participants at the time of sampling.Sex as a biological variable not detected. Randomization All samples from subjects undergoing spironolactone treatment and placebo controls were from the HOMAGE trial, a prospective, randomized, open-label, blinded-endpoint (PROBE), multicentre design, in which people at increased risk of developing HF were randomly assigned to receive either spironolactone or standard of care (“control”) - not receiving spironolactone or other mineralocorticoid receptor antagonists (ClinicalTrials.gov Identifier: NCT02556450). Blinding All samples from subjects undergoing spironolactone treatment and placebo controls were from the HOMAGE trial, a prospective, randomized, open-label, blinded-endpoint (PROBE), multicentre design, in which people at increased risk of developing HF were randomly assigned to receive either spironolactone or standard of care (“control”) - not receiving spironolactone or other mineralocorticoid receptor antagonists (ClinicalTrials.gov Identifier: NCT02556450). Power Analysis not detected. Table 2: Resources
Software and Algorithms Sentences Resources Distribution of the CoV50 scoring was evaluated using MedCalc (version 12.1.0.0, MedCalc Software, Mariakerke, Belgium; https://www.medcalc.org/). MedCalcsuggested: (MedCalc, RRID:SCR_015044)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: An explicit section about the limitations of the techniques employed in this study was not found. We encourage authors to address study limitations.Results from TrialIdentifier: We found the following clinical trial numbers in your paper:
Identifier Status Title NCT02556450 Completed Bioprofiling Response to Mineralocorticoid Receptor Antagoni… 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.
- Thank you for including a funding statement. Authors are encouraged to include this statement when submitting to a journal.
- No protocol registration statement was detected.
Results from scite Reference Check: We found no unreliable references.
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