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Comparative transcriptome analysis of SARS-CoV, MERS-CoV, and SARS-CoV-2 to identify potential pathways for drug repurposing

The ongoing COVID-19 pandemic caused by the coronavirus, SARS-CoV-2, has already caused in excess of 1.25 million deaths worldwide, and the number is increasing. Knowledge of the host transcriptional response against this virus and how the pathways are activated or suppressed compared to other human...

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Autores principales: Krishnamoorthy, Pandikannan, Raj, Athira S., Roy, Swagnik, Kumar, Nachimuthu Senthil, Kumar, Himanshu
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Elsevier Ltd. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7683955/
https://www.ncbi.nlm.nih.gov/pubmed/33260034
http://dx.doi.org/10.1016/j.compbiomed.2020.104123
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author Krishnamoorthy, Pandikannan
Raj, Athira S.
Roy, Swagnik
Kumar, Nachimuthu Senthil
Kumar, Himanshu
author_facet Krishnamoorthy, Pandikannan
Raj, Athira S.
Roy, Swagnik
Kumar, Nachimuthu Senthil
Kumar, Himanshu
author_sort Krishnamoorthy, Pandikannan
collection PubMed
description The ongoing COVID-19 pandemic caused by the coronavirus, SARS-CoV-2, has already caused in excess of 1.25 million deaths worldwide, and the number is increasing. Knowledge of the host transcriptional response against this virus and how the pathways are activated or suppressed compared to other human coronaviruses (SARS-CoV, MERS-CoV) that caused outbreaks previously can help in the identification of potential drugs for the treatment of COVID-19. Hence, we used time point meta-analysis to investigate available SARS-CoV and MERS-CoV in-vitro transcriptome datasets in order to identify the significant genes and pathways that are dysregulated at each time point. The subsequent over-representation analysis (ORA) revealed that several pathways are significantly dysregulated at each time point after both SARS-CoV and MERS-CoV infection. We also performed gene set enrichment analyses of SARS-CoV and MERS-CoV with that of SARS-CoV-2 at the same time point and cell line, the results of which revealed that common pathways are activated and suppressed in all three coronaviruses. Furthermore, an analysis of an in-vivo transcriptomic dataset of COVID-19 patients showed that similar pathways are enriched to those identified in the earlier analyses. Based on these findings, a drug repurposing analysis was performed to identify potential drug candidates for combating COVID-19.
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spelling pubmed-76839552020-11-24 Comparative transcriptome analysis of SARS-CoV, MERS-CoV, and SARS-CoV-2 to identify potential pathways for drug repurposing Krishnamoorthy, Pandikannan Raj, Athira S. Roy, Swagnik Kumar, Nachimuthu Senthil Kumar, Himanshu Comput Biol Med Article The ongoing COVID-19 pandemic caused by the coronavirus, SARS-CoV-2, has already caused in excess of 1.25 million deaths worldwide, and the number is increasing. Knowledge of the host transcriptional response against this virus and how the pathways are activated or suppressed compared to other human coronaviruses (SARS-CoV, MERS-CoV) that caused outbreaks previously can help in the identification of potential drugs for the treatment of COVID-19. Hence, we used time point meta-analysis to investigate available SARS-CoV and MERS-CoV in-vitro transcriptome datasets in order to identify the significant genes and pathways that are dysregulated at each time point. The subsequent over-representation analysis (ORA) revealed that several pathways are significantly dysregulated at each time point after both SARS-CoV and MERS-CoV infection. We also performed gene set enrichment analyses of SARS-CoV and MERS-CoV with that of SARS-CoV-2 at the same time point and cell line, the results of which revealed that common pathways are activated and suppressed in all three coronaviruses. Furthermore, an analysis of an in-vivo transcriptomic dataset of COVID-19 patients showed that similar pathways are enriched to those identified in the earlier analyses. Based on these findings, a drug repurposing analysis was performed to identify potential drug candidates for combating COVID-19. Elsevier Ltd. 2021-01 2020-11-24 /pmc/articles/PMC7683955/ /pubmed/33260034 http://dx.doi.org/10.1016/j.compbiomed.2020.104123 Text en © 2020 Elsevier Ltd. All rights reserved. Since January 2020 Elsevier has created a COVID-19 resource centre with free information in English and Mandarin on the novel coronavirus COVID-19. The COVID-19 resource centre is hosted on Elsevier Connect, the company's public news and information website. Elsevier hereby grants permission to make all its COVID-19-related research that is available on the COVID-19 resource centre - including this research content - immediately available in PubMed Central and other publicly funded repositories, such as the WHO COVID database with rights for unrestricted research re-use and analyses in any form or by any means with acknowledgement of the original source. These permissions are granted for free by Elsevier for as long as the COVID-19 resource centre remains active.
spellingShingle Article
Krishnamoorthy, Pandikannan
Raj, Athira S.
Roy, Swagnik
Kumar, Nachimuthu Senthil
Kumar, Himanshu
Comparative transcriptome analysis of SARS-CoV, MERS-CoV, and SARS-CoV-2 to identify potential pathways for drug repurposing
title Comparative transcriptome analysis of SARS-CoV, MERS-CoV, and SARS-CoV-2 to identify potential pathways for drug repurposing
title_full Comparative transcriptome analysis of SARS-CoV, MERS-CoV, and SARS-CoV-2 to identify potential pathways for drug repurposing
title_fullStr Comparative transcriptome analysis of SARS-CoV, MERS-CoV, and SARS-CoV-2 to identify potential pathways for drug repurposing
title_full_unstemmed Comparative transcriptome analysis of SARS-CoV, MERS-CoV, and SARS-CoV-2 to identify potential pathways for drug repurposing
title_short Comparative transcriptome analysis of SARS-CoV, MERS-CoV, and SARS-CoV-2 to identify potential pathways for drug repurposing
title_sort comparative transcriptome analysis of sars-cov, mers-cov, and sars-cov-2 to identify potential pathways for drug repurposing
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7683955/
https://www.ncbi.nlm.nih.gov/pubmed/33260034
http://dx.doi.org/10.1016/j.compbiomed.2020.104123
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