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In vitro Targeting of Transcription Factors to Control the Cytokine Release Syndrome in COVID-19
Treatment of the cytokine release syndrome (CRS) has become an important part of rescuing hospitalized COVID-19 patients. Here, we systematically explored the transcriptional regulators of inflammatory cytokines involved in the COVID-19 CRS to identify candidate transcription factors (TFs) for thera...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Cold Spring Harbor Laboratory
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7781316/ https://www.ncbi.nlm.nih.gov/pubmed/33398281 http://dx.doi.org/10.1101/2020.12.29.424728 |
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author | Santoso, Clarissa S. Li, Zhaorong Rottenberg, Jaice T. Liu, Xing Shen, Vivian X. Bass, Juan I. Fuxman |
author_facet | Santoso, Clarissa S. Li, Zhaorong Rottenberg, Jaice T. Liu, Xing Shen, Vivian X. Bass, Juan I. Fuxman |
author_sort | Santoso, Clarissa S. |
collection | PubMed |
description | Treatment of the cytokine release syndrome (CRS) has become an important part of rescuing hospitalized COVID-19 patients. Here, we systematically explored the transcriptional regulators of inflammatory cytokines involved in the COVID-19 CRS to identify candidate transcription factors (TFs) for therapeutic targeting using approved drugs. We integrated a resource of TF-cytokine gene interactions with single-cell RNA-seq expression data from bronchoalveolar lavage fluid cells of COVID-19 patients. We found 581 significantly correlated interactions, between 95 TFs and 16 cytokines upregulated in the COVID-19 patients, that may contribute to pathogenesis of the disease. Among these, we identified 19 TFs that are targets of FDA approved drugs. We investigated the potential therapeutic effect of 10 drugs and 25 drug combinations on inflammatory cytokine production in peripheral blood mononuclear cells, which revealed two drugs that inhibited cytokine production and numerous combinations that show synergistic efficacy in downregulating cytokine production. Further studies of these candidate repurposable drugs could lead to a therapeutic regimen to treat the CRS in COVID-19 patients. |
format | Online Article Text |
id | pubmed-7781316 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | Cold Spring Harbor Laboratory |
record_format | MEDLINE/PubMed |
spelling | pubmed-77813162021-01-05 In vitro Targeting of Transcription Factors to Control the Cytokine Release Syndrome in COVID-19 Santoso, Clarissa S. Li, Zhaorong Rottenberg, Jaice T. Liu, Xing Shen, Vivian X. Bass, Juan I. Fuxman bioRxiv Article Treatment of the cytokine release syndrome (CRS) has become an important part of rescuing hospitalized COVID-19 patients. Here, we systematically explored the transcriptional regulators of inflammatory cytokines involved in the COVID-19 CRS to identify candidate transcription factors (TFs) for therapeutic targeting using approved drugs. We integrated a resource of TF-cytokine gene interactions with single-cell RNA-seq expression data from bronchoalveolar lavage fluid cells of COVID-19 patients. We found 581 significantly correlated interactions, between 95 TFs and 16 cytokines upregulated in the COVID-19 patients, that may contribute to pathogenesis of the disease. Among these, we identified 19 TFs that are targets of FDA approved drugs. We investigated the potential therapeutic effect of 10 drugs and 25 drug combinations on inflammatory cytokine production in peripheral blood mononuclear cells, which revealed two drugs that inhibited cytokine production and numerous combinations that show synergistic efficacy in downregulating cytokine production. Further studies of these candidate repurposable drugs could lead to a therapeutic regimen to treat the CRS in COVID-19 patients. Cold Spring Harbor Laboratory 2020-12-30 /pmc/articles/PMC7781316/ /pubmed/33398281 http://dx.doi.org/10.1101/2020.12.29.424728 Text en https://creativecommons.org/licenses/by-nc/4.0/This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License (https://creativecommons.org/licenses/by-nc/4.0/) , which allows reusers to distribute, remix, adapt, and build upon the material in any medium or format for noncommercial purposes only, and only so long as attribution is given to the creator. |
spellingShingle | Article Santoso, Clarissa S. Li, Zhaorong Rottenberg, Jaice T. Liu, Xing Shen, Vivian X. Bass, Juan I. Fuxman In vitro Targeting of Transcription Factors to Control the Cytokine Release Syndrome in COVID-19 |
title | In vitro Targeting of Transcription Factors to Control the Cytokine Release Syndrome in COVID-19 |
title_full | In vitro Targeting of Transcription Factors to Control the Cytokine Release Syndrome in COVID-19 |
title_fullStr | In vitro Targeting of Transcription Factors to Control the Cytokine Release Syndrome in COVID-19 |
title_full_unstemmed | In vitro Targeting of Transcription Factors to Control the Cytokine Release Syndrome in COVID-19 |
title_short | In vitro Targeting of Transcription Factors to Control the Cytokine Release Syndrome in COVID-19 |
title_sort | in vitro targeting of transcription factors to control the cytokine release syndrome in covid-19 |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7781316/ https://www.ncbi.nlm.nih.gov/pubmed/33398281 http://dx.doi.org/10.1101/2020.12.29.424728 |
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