In silico analysis identifies possible COVID-19 cytokine storm drugs
2022
Spanish National Cancer Research Centre, Madrid, Spain
Among the causes of mortality triggered by SARS-CoV-2 infection, the development of an inflammatory “cytokine storm” (CS) plays a determinant role. Here, the researchers used transcriptomic data from the bronchoalveolar lavage fluid (BALF) of COVID-19 patients undergoing a CS to obtain gene signatures associated with this pathology. Using these signatures, they 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 whose 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, the researchers 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, they identified glucocorticoids as a top hit, which validates their approach as this is the primary treatment for this pathology. Interestingly, the 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.
An in silico analysis identifies drugs potentially modulating the cytokine storm triggered by SARS-CoV-2 infection
Oscar Fernandez-Capetillo
Added on: 03-16-2022
[1] https://www.nature.com/articles/s41598-022-05597-x[2] https://www.drugtargetreview.com/news/101141/researchers-identify-potential-drugs-to-reduce-covid-19-mortalities/?utm_source=Email+marketing&utm_medium=email&utm_campaign=DTR+-+Newsletter+6+-+Metabolon+-+10.02.2022&utm_term=Novel+CAR+T-cell+therapy+for+B-cell+cancers+shows+promise+in+vivo&utm_content=https%3a%2f%2femails.drugtargetreview.com%2frussellpublishinglz%2f&gator_td=sORP3zbNdMyc2lO7iTcQAmfg67Hr5kDgn3NHG%2bLXhn0qD0%2f0xlXtY1xhjY8TAm7fQ%2brvedI7P8kFRaATmU7E1MKq2Ev5tA3%2fUgO4TQyHa7vfT%2fjS96sgd1PJmKrgjkTPawdYFy3QcfD07jA3%2f3%2fLGUFcuzhpRioCWYhzwXUVaMH5Fed5YXGrxNx9XcluRUC0IozBGRQNUXIJqNp0ZXTw4avhem%2feNcuVBMCLAhgiijY%3d
