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  1. Article ; Online: Natural selection plays a significant role in governing the codon usage bias in the novel SARS-CoV-2 variants of concern (VOC)

    Neetu Tyagi / Rahila Sardar / Dinesh Gupta

    PeerJ, Vol 10, p e

    2022  Volume 13562

    Abstract: The ongoing prevailing COVID-19 pandemic caused by SARS-CoV-2 is becoming one of the major global health concerns worldwide. The SARS-CoV-2 genome encodes spike (S) glycoprotein that plays a very crucial role in viral entry into the host cell via binding ...

    Abstract The ongoing prevailing COVID-19 pandemic caused by SARS-CoV-2 is becoming one of the major global health concerns worldwide. The SARS-CoV-2 genome encodes spike (S) glycoprotein that plays a very crucial role in viral entry into the host cell via binding of its receptor binding domain (RBD) to the host angiotensin converting enzyme 2 (ACE2) receptor. The continuously evolving SARS-CoV-2 genome results in more severe and transmissible variants characterized by the emergence of novel mutations called ‘variants of concern’ (VOC). The currently designated alpha, beta, gamma, delta and omicron VOC are the focus of this study due to their high transmissibility, increased virulence, and concerns for decreased effectiveness of the available vaccines. In VOC, the spike (S) gene and other non-structural protein mutations may affect the efficacies of the approved COVID-19 vaccines. To understand the diversity of SARS-CoV-2, several studies have been performed on a limited number of sequences. However, only a few studies have focused on codon usage bias (CUBs) pattern analysis of all the VOC strains. Therefore, to evaluate the evolutionary divergence of all VOC S-genes, we performed CUBs analysis on 300,354 sequences to understand the evolutionary relationship with its adaptation in different hosts, i.e., humans, bats, and pangolins. Base composition and RSCU analysis revealed the presence of 20 preferred AU-ended and 10 under-preferred GC-ended codons. In addition, CpG was found to be depleted, which may be attributable to the adaptive response by viruses to escape from the host defense process. Moreover, the ENC values revealed a higher bias in codon usage in the VOC S-gene. Further, the neutrality plot analysis demonstrated that S-genes analyzed in this study are under 83.93% influence of natural selection, suggesting its pivotal role in shaping the CUBs. The CUBs pattern of S-genes was found to be very similar among all the VOC strains. Interestingly, we observed that VOC strains followed a trend of antagonistic codon ...
    Keywords Codon usage bias ; Mutational pressure ; Natural selection ; Variants of concern (VOC) ; SARS-CoV-2 ; Medicine ; R ; Biology (General) ; QH301-705.5
    Subject code 570 ; 572
    Language English
    Publishing date 2022-06-01T00:00:00Z
    Publisher PeerJ Inc.
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  2. Article ; Online: Dataset of mutational analysis, miRNAs targeting SARS-CoV-2 genes and host gene expression in SARS-CoV and SARS-CoV-2 infections

    Rahila Sardar / Deepshikha Satish / Shweta Birla / Dinesh Gupta

    Data in Brief, Vol 32, Iss , Pp 106207- (2020)

    2020  

    Abstract: The identification of host-miRNAs targeting mutated virus genes is crucial to understand the miRNA mediated host-defense mechanism in virus infections. To understand the mechanism in COVID-19 infections, we collected genome sequences of SARS-CoV-2 with ... ...

    Abstract The identification of host-miRNAs targeting mutated virus genes is crucial to understand the miRNA mediated host-defense mechanism in virus infections. To understand the mechanism in COVID-19 infections, we collected genome sequences of SARS-CoV-2 with its metadata from the GISAID database (submitted till April 2020) and identified mutational changes in the sequences. The dataset consists of genes with mutation event count and entropy scores. We predicted host-miRNAs targeting the genes in the genomes and compared it with that in related viral species. We have identified 2284 miRNAs targeting MERS genomes, 2074 miRNAs targeting SARS genomes, and 1599 miRNAs targeting SARS-CoV-2 genomes, identified using the miRNA target prediction software miRanda. The host miRNAs targeting SARS-CoV-2 genes were further validated to be anti-viral miRNAs and their role in respiratory diseases through a literature survey, which helped in the identification of 42 conserved antiviral miRNAs. The data could be used to validate the anti-viral role of the predicted miRNAs and design miRNA-based therapeutics against SARS-CoV-2.
    Keywords COVID-19 ; Mutation ; Antiviral ; miRNA ; Gene expression ; Computer applications to medicine. Medical informatics ; R858-859.7 ; Science (General) ; Q1-390
    Subject code 572
    Language English
    Publishing date 2020-10-01T00:00:00Z
    Publisher Elsevier
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  3. Book ; Online: Table_5_Identification of Novel SARS-CoV-2 Drug Targets by Host MicroRNAs and Transcription Factors Co-regulatory Interaction Network Analysis.XLSX

    Rahila Sardar / Deepshikha Satish / Dinesh Gupta

    2020  

    Abstract: 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 ... ...

    Abstract 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.
    Keywords Genetics ; Genetic Engineering ; Biomarkers ; Developmental Genetics (incl. Sex Determination) ; Epigenetics (incl. Genome Methylation and Epigenomics) ; Gene Expression (incl. Microarray and other genome-wide approaches) ; Genome Structure and Regulation ; Genomics ; Genetically Modified Animals ; Livestock Cloning ; Gene and Molecular Therapy ; regulatory network ; miRNA ; SARS-CoV-2 ; hub genes ; TFS ; covid19
    Subject code 570 ; 572
    Publishing date 2020-10-14T04:45:28Z
    Publishing country uk
    Document type Book ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  4. Book ; Online: Table_8_Identification of Novel SARS-CoV-2 Drug Targets by Host MicroRNAs and Transcription Factors Co-regulatory Interaction Network Analysis.xls

    Rahila Sardar / Deepshikha Satish / Dinesh Gupta

    2020  

    Abstract: 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 ... ...

    Abstract 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.
    Keywords Genetics ; Genetic Engineering ; Biomarkers ; Developmental Genetics (incl. Sex Determination) ; Epigenetics (incl. Genome Methylation and Epigenomics) ; Gene Expression (incl. Microarray and other genome-wide approaches) ; Genome Structure and Regulation ; Genomics ; Genetically Modified Animals ; Livestock Cloning ; Gene and Molecular Therapy ; regulatory network ; miRNA ; SARS-CoV-2 ; hub genes ; TFS ; covid19
    Subject code 570 ; 572
    Publishing date 2020-10-14T04:45:29Z
    Publishing country uk
    Document type Book ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  5. Book ; Online: Table_4_Identification of Novel SARS-CoV-2 Drug Targets by Host MicroRNAs and Transcription Factors Co-regulatory Interaction Network Analysis.XLSX

    Rahila Sardar / Deepshikha Satish / Dinesh Gupta

    2020  

    Abstract: 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 ... ...

    Abstract 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.
    Keywords Genetics ; Genetic Engineering ; Biomarkers ; Developmental Genetics (incl. Sex Determination) ; Epigenetics (incl. Genome Methylation and Epigenomics) ; Gene Expression (incl. Microarray and other genome-wide approaches) ; Genome Structure and Regulation ; Genomics ; Genetically Modified Animals ; Livestock Cloning ; Gene and Molecular Therapy ; regulatory network ; miRNA ; SARS-CoV-2 ; hub genes ; TFS ; covid19
    Subject code 570 ; 572
    Publishing date 2020-10-14T04:45:28Z
    Publishing country uk
    Document type Book ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  6. Book ; Online: Table_1_Identification of Novel SARS-CoV-2 Drug Targets by Host MicroRNAs and Transcription Factors Co-regulatory Interaction Network Analysis.XLSX

    Rahila Sardar / Deepshikha Satish / Dinesh Gupta

    2020  

    Abstract: 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 ... ...

    Abstract 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.
    Keywords Genetics ; Genetic Engineering ; Biomarkers ; Developmental Genetics (incl. Sex Determination) ; Epigenetics (incl. Genome Methylation and Epigenomics) ; Gene Expression (incl. Microarray and other genome-wide approaches) ; Genome Structure and Regulation ; Genomics ; Genetically Modified Animals ; Livestock Cloning ; Gene and Molecular Therapy ; regulatory network ; miRNA ; SARS-CoV-2 ; hub genes ; TFS ; covid19
    Subject code 570 ; 572
    Publishing date 2020-10-14T04:45:27Z
    Publishing country uk
    Document type Book ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  7. Book ; Online: Table_6_Identification of Novel SARS-CoV-2 Drug Targets by Host MicroRNAs and Transcription Factors Co-regulatory Interaction Network Analysis.xlsx

    Rahila Sardar / Deepshikha Satish / Dinesh Gupta

    2020  

    Abstract: 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 ... ...

    Abstract 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.
    Keywords Genetics ; Genetic Engineering ; Biomarkers ; Developmental Genetics (incl. Sex Determination) ; Epigenetics (incl. Genome Methylation and Epigenomics) ; Gene Expression (incl. Microarray and other genome-wide approaches) ; Genome Structure and Regulation ; Genomics ; Genetically Modified Animals ; Livestock Cloning ; Gene and Molecular Therapy ; regulatory network ; miRNA ; SARS-CoV-2 ; hub genes ; TFS ; covid19
    Subject code 570 ; 572
    Publishing date 2020-10-14T04:45:29Z
    Publishing country uk
    Document type Book ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  8. Article ; Online: Identification of Novel SARS-CoV-2 Drug Targets by Host MicroRNAs and Transcription Factors Co-regulatory Interaction Network Analysis

    Rahila Sardar / Deepshikha Satish / Dinesh Gupta

    Frontiers in Genetics, Vol

    2020  Volume 11

    Abstract: 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 ... ...

    Abstract 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.
    Keywords regulatory network ; miRNA ; SARS-CoV-2 ; hub genes ; TFS ; Genetics ; QH426-470 ; covid19
    Subject code 570 ; 572
    Language English
    Publishing date 2020-10-01T00:00:00Z
    Publisher Frontiers Media S.A.
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  9. Book ; Online: Table_7_Identification of Novel SARS-CoV-2 Drug Targets by Host MicroRNAs and Transcription Factors Co-regulatory Interaction Network Analysis.xlsx

    Rahila Sardar / Deepshikha Satish / Dinesh Gupta

    2020  

    Abstract: 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 ... ...

    Abstract 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.
    Keywords Genetics ; Genetic Engineering ; Biomarkers ; Developmental Genetics (incl. Sex Determination) ; Epigenetics (incl. Genome Methylation and Epigenomics) ; Gene Expression (incl. Microarray and other genome-wide approaches) ; Genome Structure and Regulation ; Genomics ; Genetically Modified Animals ; Livestock Cloning ; Gene and Molecular Therapy ; regulatory network ; miRNA ; SARS-CoV-2 ; hub genes ; TFS ; covid19
    Subject code 570 ; 572
    Publishing date 2020-10-14T04:45:29Z
    Publishing country uk
    Document type Book ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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    Kategorien

  10. Book ; Online: Table_2_Identification of Novel SARS-CoV-2 Drug Targets by Host MicroRNAs and Transcription Factors Co-regulatory Interaction Network Analysis.xlsx

    Rahila Sardar / Deepshikha Satish / Dinesh Gupta

    2020  

    Abstract: 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 ... ...

    Abstract 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.
    Keywords Genetics ; Genetic Engineering ; Biomarkers ; Developmental Genetics (incl. Sex Determination) ; Epigenetics (incl. Genome Methylation and Epigenomics) ; Gene Expression (incl. Microarray and other genome-wide approaches) ; Genome Structure and Regulation ; Genomics ; Genetically Modified Animals ; Livestock Cloning ; Gene and Molecular Therapy ; regulatory network ; miRNA ; SARS-CoV-2 ; hub genes ; TFS ; covid19
    Subject code 570 ; 572
    Publishing date 2020-10-14T04:45:28Z
    Publishing country uk
    Document type Book ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

    More links

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