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Identification of Novel SARS-CoV-2 Drug Targets by Host MicroRNAs and Transcription Factors Co-regulatory Interaction Network Analysis

Understanding the host regulatory mechanisms opposing virus infection and virulence can provide actionable insights to identify novel therapeutics against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We have used a network biology approach to elucidate the crucial factors involved i...

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Autores principales: Sardar, Rahila, Satish, Deepshikha, Gupta, Dinesh
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7591747/
https://www.ncbi.nlm.nih.gov/pubmed/33173539
http://dx.doi.org/10.3389/fgene.2020.571274
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author Sardar, Rahila
Satish, Deepshikha
Gupta, Dinesh
author_facet Sardar, Rahila
Satish, Deepshikha
Gupta, Dinesh
author_sort Sardar, Rahila
collection PubMed
description Understanding the host regulatory mechanisms opposing virus infection and virulence can provide actionable insights to identify novel therapeutics against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We have used a network biology approach to elucidate the crucial factors involved in host responses involving host–microRNA (miRNA) interactions with host and virus genes using recently published experimentally verified protein–protein interaction data. We were able to identify 311 host genes to be potentially targetable by 2,197 human miRNAs. These miRNAs are known to be involved in various biological processes, such as T-cell differentiation and activation, virus replication, and immune system. Among these, the anti-viral activity of 38 miRNAs to target 148 host genes is experimentally validated. Six anti-viral miRNAs, namely, hsa-miR-1-3p, hsa-miR-17-5p, hsa-miR-199a-3p, hsa-miR-429, hsa-miR-15a-5p, and hsa-miR-20a-5p, are previously reported to be anti-viral in respiratory diseases and were found to be downregulated. The interaction network of the 2,197 human miRNAs and interacting transcription factors (TFs) enabled the identification of 51 miRNAs to interact with 77 TFs inducing activation or repression and affecting gene expression of linked genes. Further, from the gene regulatory network analysis, the top five hub genes HMOX1, DNMT1, PLAT, GDF1, and ITGB1 are found to be involved in interferon (IFN)-α2b induction, epigenetic modification, and modulation of anti-viral activity. The comparative miRNAs target identification analysis in other respiratory viruses revealed the presence of 98 unique host miRNAs targeting SARS-CoV-2 genome. Our findings identify prioritized key regulatory interactions that include miRNAs and TFs that provide opportunities for the identification of novel drug targets and development of anti-viral drugs.
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spelling pubmed-75917472020-11-09 Identification of Novel SARS-CoV-2 Drug Targets by Host MicroRNAs and Transcription Factors Co-regulatory Interaction Network Analysis Sardar, Rahila Satish, Deepshikha Gupta, Dinesh Front Genet Genetics Understanding the host regulatory mechanisms opposing virus infection and virulence can provide actionable insights to identify novel therapeutics against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We have used a network biology approach to elucidate the crucial factors involved in host responses involving host–microRNA (miRNA) interactions with host and virus genes using recently published experimentally verified protein–protein interaction data. We were able to identify 311 host genes to be potentially targetable by 2,197 human miRNAs. These miRNAs are known to be involved in various biological processes, such as T-cell differentiation and activation, virus replication, and immune system. Among these, the anti-viral activity of 38 miRNAs to target 148 host genes is experimentally validated. Six anti-viral miRNAs, namely, hsa-miR-1-3p, hsa-miR-17-5p, hsa-miR-199a-3p, hsa-miR-429, hsa-miR-15a-5p, and hsa-miR-20a-5p, are previously reported to be anti-viral in respiratory diseases and were found to be downregulated. The interaction network of the 2,197 human miRNAs and interacting transcription factors (TFs) enabled the identification of 51 miRNAs to interact with 77 TFs inducing activation or repression and affecting gene expression of linked genes. Further, from the gene regulatory network analysis, the top five hub genes HMOX1, DNMT1, PLAT, GDF1, and ITGB1 are found to be involved in interferon (IFN)-α2b induction, epigenetic modification, and modulation of anti-viral activity. The comparative miRNAs target identification analysis in other respiratory viruses revealed the presence of 98 unique host miRNAs targeting SARS-CoV-2 genome. Our findings identify prioritized key regulatory interactions that include miRNAs and TFs that provide opportunities for the identification of novel drug targets and development of anti-viral drugs. Frontiers Media S.A. 2020-10-14 /pmc/articles/PMC7591747/ /pubmed/33173539 http://dx.doi.org/10.3389/fgene.2020.571274 Text en Copyright © 2020 Sardar, Satish and Gupta. http://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 Genetics
Sardar, Rahila
Satish, Deepshikha
Gupta, Dinesh
Identification of Novel SARS-CoV-2 Drug Targets by Host MicroRNAs and Transcription Factors Co-regulatory Interaction Network Analysis
title Identification of Novel SARS-CoV-2 Drug Targets by Host MicroRNAs and Transcription Factors Co-regulatory Interaction Network Analysis
title_full Identification of Novel SARS-CoV-2 Drug Targets by Host MicroRNAs and Transcription Factors Co-regulatory Interaction Network Analysis
title_fullStr Identification of Novel SARS-CoV-2 Drug Targets by Host MicroRNAs and Transcription Factors Co-regulatory Interaction Network Analysis
title_full_unstemmed Identification of Novel SARS-CoV-2 Drug Targets by Host MicroRNAs and Transcription Factors Co-regulatory Interaction Network Analysis
title_short Identification of Novel SARS-CoV-2 Drug Targets by Host MicroRNAs and Transcription Factors Co-regulatory Interaction Network Analysis
title_sort identification of novel sars-cov-2 drug targets by host micrornas and transcription factors co-regulatory interaction network analysis
topic Genetics
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7591747/
https://www.ncbi.nlm.nih.gov/pubmed/33173539
http://dx.doi.org/10.3389/fgene.2020.571274
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