2026-06-14T03:37:37Zhttps://repisalud.isciii.es/rest/oai/requestoai:repisalud.isciii.es:20.500.12105/136092024-11-29T22:30:29Zcom_20.500.12105_2173com_20.500.12105_2051col_20.500.12105_19597
Repisalud
author
Sanchez-Burgos, Laura
author
Gómez-López, Gonzalo
author
Al-Shahrour, Fatima
author
Fernandez-Capetillo, Oscar
funder
Karolinska Institutet
2022-02-02T09:21:24Z
2022-02-02T09:21:24Z
2022-01-31
Sci Rep. 2022; in press
10.1038/s41598-022-05597-x
2045-2322
Scientific Reports
http://hdl.handle.net/20.500.12105/13609
The ongoing COVID-19 pandemic is one of the biggest health challenges of recent decades. Among the causes of mortality triggered by SARS-CoV-2 infection, the development of an inflammatory “cytokine storm” (CS) plays a determinant role. Here, we used transcriptomic data from the bronchoalveolar lavage fluid (BALF) of COVID-19 patients undergoing a CS to obtain gene-signatures associated to this pathology. Using these signatures, we interrogated the Connectivity Map (CMap) dataset that contains the effects of over 5000 small molecules on the transcriptome of human cell lines, and looked for molecules which effects on transcription mimic or oppose those of the CS. As expected, molecules that potentiate immune responses such as PKC activators are predicted to worsen the CS. In addition, we identified the negative regulation of female hormones among pathways potentially aggravating the CS, which helps to understand the gender-related differences in COVID-19 mortality. Regarding drugs potentially counteracting the CS, we identified glucocorticoids as a top hit, which validates our approach as this is the primary treatment for this pathology. Interestingly, our analysis also reveals a potential effect of MEK inhibitors in reverting the COVID-19 CS, which is supported by in vitro data that confirms the anti-inflammatory properties of these compounds.
eng
An in silico analysis identifies drugs potentially modulating the cytokine storm triggered by SARS-CoV-2 infection
journal article
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