SGLT2-Inhibition reverts urinary peptide changes associated with severe COVID-19: an in-silico proof-of-principle of proteomics-based drug repurposing
A. Latosinska, J. Siwy, D. Cherney
Jul 22, 2021
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Quality indicators
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Semantic Scholar
Key Takeaway Key Takeaway: SGLT2-Inhibition significantly reverses urinary peptide changes associated with severe COVID-19, suggesting potential therapeutic benefits for COVID-19 treatment.
Abstract
Severe COVID-19 is reflected by significant changes in multiple urine peptides. Based on this observation, a clinical test based on urinary peptides predicting COVID-19 severity, CoV50, was developed and registered as IVD in Germany. We have hypothesized that molecular changes displayed by CoV50, to a large degree likely reflective of endothelial damage, can be significantly reversed by specific drugs. To test this hypothesis, we have collected urinary peptide data from patients without COVID-19 prior and after drug treatment. 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, while 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 results serve as a proof-of-principle for a drug repurposing approach based on human urinary peptide signatures and support the initiation of a randomised control trial testing a potential positive effect of empagliflozin in the treatment of severe COVID-19, possibly via endothelial protective mechanisms.