Black List Acid Black Cherry Rar
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Enriched targets and mechanisms of action of potential antiviral compounds were determined through GSEA. GSEA enrichment plots provide the distribution of the enrichment score (green line) across compounds that were annotated to molecular targets, ranked in order of antiviral activities (left to right). Vertical black lines reflect the position of each compound within a specific target class across the ranked dataset, where the leftmost position indicates most potent antiviral activity (red), and the rightmost position indicates inactivity in the HTS screen (blue). Enriched target clusters are shown, including retinoic acid receptor agonists, benzodiazepine receptor inhibitors, aldose reductase agonists, potassium channel agonists, cholesterol inhibitors and antimalarials (P
These data suggest to us that RAR inhibition in our screen might be a result of an integrated response, with early treatments causing a local and potent antiviral response, and late treatment causing a more global cellular antiviral response. Because of the observed phenotype, we can only speculate that RAR inhibition may potentiate the cytotoxicity of other compounds, as a result of diminished antiviral defenses as a consequence of early inhibition. This is plausible considering that we observed increased cellular death at earlier time points after SARS-CoV-2 infection as compared to mock infection. However, we acknowledge that the kinetics of cellular responses after viral infection and the implications of drug-induced responses to SARS-CoV-2 are not clear. d2c66b5586