Identification of potential mRNA panels for severe acute respiratory syndrome coronavirus 2 (COVID-19) diagnosis and treatment using microarray dataset and bioinformatics methods

Vastrad, Basavaraj; Vastrad, Chanabasayya; Tengli, Anandkumar

doi:10.1007/s13205-020-02406-y

Cited by 37 publications

(36 citation statements)

References 198 publications

(214 reference statements)

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“… India To understand the mechanisms of SARS-CoV-2 infection and identify potential novel diagnostic or therapeutic targets through bioinformatics analysis including miRNA regulatory networks. ( Vastrad et al, 2020 ) 21 Maitra A June 4, 2020. India To provide information on the prevalence of different viral SARS-CoV-2 clades regional differences and potential human miRNA binding sites affected by mutations of the virus by sequencing the SARS-CoV-2 genome.…”

Section: Resultsmentioning

confidence: 99%

“… miR-922 PI3 GO molecular function: endopeptidase inhibitor activity, peptidase inhibitor activity, endopeptidase regulator activity Taz et al, 2020 , PDCD1 This protein was found upregulated in SARS-CoV-2 infected samples. Vastrad et al, 2020 . KEGG pathways: T cell receptor signaling pathway, Adaptative Immune system GO: regulation of immune system process, T cell activation, leukocyte activation, cell activation miR-326 S100A8 Go biological process: leukocyte aggregation, defense response to fungus, neutrophil chemotaxis, granulocyte chemotaxis, neutrophil migration Taz et al, 2020 .…”

Section: Resultsmentioning

confidence: 99%

“… KEGG pathways: T cell receptor signaling pathway, Adaptative Immune system GO: regulation of immune system process, T cell activation, leukocyte activation, cell activation miR-326 S100A8 Go biological process: leukocyte aggregation, defense response to fungus, neutrophil chemotaxis, granulocyte chemotaxis, neutrophil migration Taz et al, 2020 . KEGG pathway: IL17 signaling pathway C1R GO: innate immune system, regulation of immune system process, cytokine-mediated signaling pathway, response to biotic stimulus Vastrad et al, 2020 . …”

Section: Resultsmentioning

confidence: 99%

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The role of microRNAs in modulating SARS-CoV-2 infection in human cells: a systematic review

Marchi¹,

Sugita²,

Centa³

et al. 2021

Infection, Genetics and Evolution

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MicroRNAs are gene expression regulators, associated with several human pathologies, including the ones caused by virus infections. Although their role in infection diseases is not completely known, they can exert double functions in the infected cell, by mediating the virus infection and/or regulating the immunity-related gene targets through complex networks of virus-host cell interactions. In this systematic review, the Pubmed, EMBASE, Scopus, Lilacs, Scielo, and EBSCO databases were searched for research articles published until October 22nd, 2020 that focused on describing the role, function, and/or association of miRNAs in SARS-CoV-2 human infection and COVID-19. Following the PRISMA 2009 protocol, 29 original research articles were selected. Most of the studies reported miRNA data based on the genome sequencing of SARS-CoV-2 isolates and computational prediction analysis. The latter predicted, by at least one independent study, 1266 host miRNAs to target the viral genome. Thirteen miRNAs were identified by four independent studies to target SARS-CoV-2 specific genes, suggested to act by interfering with their cleavage and/or translation process. The studies selected also reported on viral and host miRNAs that targeted host genes, on the expression levels of miRNAs in biological specimens of COVID-19 patients, and on the impact of viral genome mutations on miRNA function. Also, miRNAs that regulate the expression levels of the ACE2 and TMPRSS2 proteins, which are critical for the virus entrance in the host cells, were reported. In conclusion, despite the limited number of studies identified, based on the search terms and eligibility criteria applied, this systematic review provides evidence on the impact of miRNAs on SARS-CoV-2 infection and COVID-19. Although most of the reported viral/host miRNAs interactions were based on in silico prediction analysis, they demonstrate the relevance of the viral/host miRNA interaction for viral activity and host responses. In addition, the identified studies highlight the potential use of miRNAs as therapeutic targets against COVID-19, and other viral human diseases (This review was registered at the International Prospective Register of Systematic Reviews (PROSPERO) database (#CRD42020199290).

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

See 1 more Smart Citation

The role of microRNAs in modulating SARS-CoV-2 infection in human cells: a systematic review

Marchi¹,

Sugita²,

Centa³

et al. 2021

Infection, Genetics and Evolution

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“…As has been demonstrated by the clinical responses to the COVID-19 pandemic, patient risk stratification can be a powerful tool in informing optimal resource management practices (staffing, therapeutics, etc.) [ 73 , 74 ]. In a second scenario, these miRNAs could be used for monitoring convalescent EVD patients for signs of long-term disease sequelae.…”

Section: Discussionmentioning

confidence: 99%

Transcriptomic Analysis Reveals Host miRNAs Correlated with Immune Gene Dysregulation during Fatal Disease Progression in the Ebola Virus Cynomolgus Macaque Disease Model

et al. 2021

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Ebola virus is a continuing threat to human populations, causing a virulent hemorrhagic fever disease characterized by dysregulation of both the innate and adaptive host immune responses. Severe cases are distinguished by an early, elevated pro-inflammatory response followed by a pronounced lymphopenia with B and T cells unable to mount an effective anti-viral response. The precise mechanisms underlying the dysregulation of the host immune system are poorly understood. In recent years, focus on host-derived miRNAs showed these molecules to play an important role in the host gene regulation arsenal. Here, we describe an investigation of RNA biomarkers in the fatal Ebola virus disease (EVD) cynomolgus macaque model. We monitored both host mRNA and miRNA responses in whole blood longitudinally over the disease course in these non-human primates (NHPs). Analysis of the interactions between these classes of RNAs revealed several miRNA markers significantly correlated with downregulation of genes; specifically, the analysis revealed those involved in dysregulated immune pathways associated with EVD. In particular, we noted strong interactions between the miRNAs hsa-miR-122-5p and hsa-miR-125b-5p with immunological genes regulating both B and T-cell activation. This promising set of biomarkers will be useful in future studies of severe EVD pathogenesis in both NHPs and humans and may serve as potential prognostic targets.

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“…SNX-5422 dampened expression of cellular genes, previously shown to be associated with SARS-CoV-2 -mediated proinflammatory response and hyper-cytokinemia (Figure 3B). Specifically, these inflammatory genes could be broadly categorized into chemokines ( CXCL1 (Coperchini et al, 2020) , CXCL5 (Coperchini et al, 2020) , CXCL6 (Blanco-Melo et al, 2020) , CXCL3 (Blanco-Melo et al, 2020) and CXCL2 (Zhou et al, 2020a)), chemokine-receptor ligands ( CCL20 (Zhou et al, 2020a) , CX3CL1 (Nienhold et al, 2020)), cytokines ( IL36G (Xiong et al, 2020)), interleukins ( IL-19 (Vastrad et al, 2020) , CXCL8 (Zhou et al, 2020a) , IL-32 (Blanco-Melo et al, 2020)), tumor necrosis factor alpha-induced protein ( TNFAIP2 (Fagone et al, 2020)), regulators of inflammatory responses ( CSF3 (Nunnari et al, 2020) , S100A8 (Zhou et al, 2020a) , S100A9 (Zhou et al, 2020a) , SCGB3A1 (Mick et al, 2020) , S100A2 (Xu et al, 2020)) and interferon-induced proteins ( RSAD2 (Zhou et al, 2020a), IFI44L (Mick et al, 2020), IFITM1 (Zhou et al, 2020a) , MX2 (Lieberman et al, 2020), IFI27 ( Mick et al, 2020) , ISG15 (Zhou et al, 2020a) ). Collectively, our analysis suggests that early treatment with SNX-5422 may mitigate SARS-CoV-2-mediated hyperinflammation, thereby improving clinical outcomes of COVID-19.…”

Section: Resultsmentioning

confidence: 99%

Oral Hsp90 inhibitor, SNX-5422, attenuates SARS-CoV-2 replication and dampens inflammation in airway cells

Goswami

Russell

et al. 2021

Preprint

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Currently available SARS-CoV-2 therapeutics are targeted towards moderately to severely ill patients and require intravenous infusions, with limited options for exposed or infected patients with no or mild symptoms. While vaccines have demonstrated protective efficacy, vaccine hesitancy and logistical distribution challenges will delay their ability to end the pandemic. Hence, there is a need for rapidly translatable, easy-to-administer-therapeutics, that can prevent SARS-CoV-2 disease progression, when administered in the early stages of infection. We demonstrate that an orally bioavailable Hsp90 inhibitor, SNX-5422, currently in clinical trials as an anti-cancer therapeutic, inhibits SARS-CoV-2 replication in vitro at a high selectivity index. SNX-5422 treatment of human primary airway epithelial cells dampened expression of inflammatory pathways associated with poor SARS-CoV-2 disease outcomes. Additionally, SNX-5422 interrupted expression of host factors that are crucial for SARS-CoV-2 replication machinery. Development of SNX-5422 as SARS-CoV-2-early-therapy will dampen disease severity, resulting in better clinical outcomes and reduced hospitalizations.

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Identification of potential mRNA panels for severe acute respiratory syndrome coronavirus 2 (COVID-19) diagnosis and treatment using microarray dataset and bioinformatics methods

Cited by 37 publications

References 198 publications

The role of microRNAs in modulating SARS-CoV-2 infection in human cells: a systematic review

The role of microRNAs in modulating SARS-CoV-2 infection in human cells: a systematic review

Transcriptomic Analysis Reveals Host miRNAs Correlated with Immune Gene Dysregulation during Fatal Disease Progression in the Ebola Virus Cynomolgus Macaque Disease Model

Oral Hsp90 inhibitor, SNX-5422, attenuates SARS-CoV-2 replication and dampens inflammation in airway cells

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