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Therapeutic 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: |
Frontiers Media S.A.
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8215608/ https://www.ncbi.nlm.nih.gov/pubmed/34163359 http://dx.doi.org/10.3389/fphar.2021.673485 |
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author | Santoso, Clarissa S. Li, Zhaorong Rottenberg, Jaice T. Liu, Xing Shen, Vivian X. Fuxman Bass, Juan I. |
author_facet | Santoso, Clarissa S. Li, Zhaorong Rottenberg, Jaice T. Liu, Xing Shen, Vivian X. Fuxman Bass, Juan I. |
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 drugs combinations on inflammatory cytokine production, 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-8215608 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-82156082021-06-22 Therapeutic 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. Fuxman Bass, Juan I. Front Pharmacol Pharmacology 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 drugs combinations on inflammatory cytokine production, 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. Frontiers Media S.A. 2021-06-07 /pmc/articles/PMC8215608/ /pubmed/34163359 http://dx.doi.org/10.3389/fphar.2021.673485 Text en Copyright © 2021 Santoso, Li, Rottenberg, Liu, Shen and Fuxman Bass. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Pharmacology Santoso, Clarissa S. Li, Zhaorong Rottenberg, Jaice T. Liu, Xing Shen, Vivian X. Fuxman Bass, Juan I. Therapeutic Targeting of Transcription Factors to Control the Cytokine Release Syndrome in COVID-19 |
title | Therapeutic Targeting of Transcription Factors to Control the Cytokine Release Syndrome in COVID-19 |
title_full | Therapeutic Targeting of Transcription Factors to Control the Cytokine Release Syndrome in COVID-19 |
title_fullStr | Therapeutic Targeting of Transcription Factors to Control the Cytokine Release Syndrome in COVID-19 |
title_full_unstemmed | Therapeutic Targeting of Transcription Factors to Control the Cytokine Release Syndrome in COVID-19 |
title_short | Therapeutic Targeting of Transcription Factors to Control the Cytokine Release Syndrome in COVID-19 |
title_sort | therapeutic targeting of transcription factors to control the cytokine release syndrome in covid-19 |
topic | Pharmacology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8215608/ https://www.ncbi.nlm.nih.gov/pubmed/34163359 http://dx.doi.org/10.3389/fphar.2021.673485 |
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