Identification of Novel Hypothalamic MicroRNAs as Promising Therapeutics for SARS-CoV-2 by Regulating ACE2 and TMPRSS2 Expression: An In Silico Analysis

Mukhopadhyay, Debasmita; Mussa, Bashair M

doi:10.3390/brainsci10100666

Cited by 35 publications

(36 citation statements)

References 71 publications

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“… Repressed transcription of miR-125a-5p as a result of JARID1B action increases ACE2 protein expression levels. let-7a-5p TMPRSS2 Expression negatively correlated with TMPRSS2 expression Mukhopadhyay and Mussa, 2020 , Nersisyan et al, 2020b . Target the 3’UTR sequence of TMPRSS2 mRNA let-7d-5p TMPRSS2 Expression negatively correlated with TMPRSS2 expression Target the 3’UTR sequence of TMPRSS2 mRNA Mukhopadhyay and Mussa, 2020 , Nersisyan et al, 2020b .…”

Section: Resultsmentioning

confidence: 94%

“… let-7a-5p TMPRSS2 Expression negatively correlated with TMPRSS2 expression Mukhopadhyay and Mussa, 2020 , Nersisyan et al, 2020b . Target the 3’UTR sequence of TMPRSS2 mRNA let-7d-5p TMPRSS2 Expression negatively correlated with TMPRSS2 expression Target the 3’UTR sequence of TMPRSS2 mRNA Mukhopadhyay and Mussa, 2020 , Nersisyan et al, 2020b . 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.…”

Section: Resultsmentioning

confidence: 94%

“… ( Zhang et al, 2020 ) 26 Mukhopadhyay D September 25, 2020. United Arab Emirates To investigate the miRNAs that regulate the expression of ACE2 and TMPRSS2, essential elements for SARS-CoV-2 infection ( Mukhopadhyay and Mussa, 2020 ) 27 Nersisyan SA April 29, 2020. Russia To investigate the mechanisms of the interaction between miRNA isoforms and ACE2/TMPRSS2 genes in the colon tissue of COVID-19 patients ( Nersisyan et al, 2020c ) 28 Nersisyan S b July 29, 2020.…”

Section: Resultsmentioning

confidence: 99%

“…Among these miRNAs, miR-1246, miR-200c-3p, and miR-125a-5p were predicted as potential regulators of ACE2 expression, with their interactions functionally validated or expressions negatively correlated ( Khan et al, 2020a , Lu et al, 2020 , Nersisyan et al, 2020b , Nersisyan et al, 2020c , Zhang et al, 2020 ). Let-7a-5p and let-7d-5p were predicted to target TMPRSS2, however, its interaction remains to be validated ( Mukhopadhyay and Mussa, 2020 ; Nersisyan et al, 2020b ).…”

Section: Discussionmentioning

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: 94%

Section: Resultsmentioning

confidence: 94%

Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

See 2 more Smart Citations

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

View full text Add to dashboard Cite

show abstract

“…Similarly, the ACE2 receptor was suppressed by targeting its 3' UTR gene by hsa-miR-23b-5p and hsa-miR-769-5p [35]. 31 miRNAs and 29 miRNAs can downregulate hypothalamic ACE2 and TMPRSS2 gene expression, respectively, suggesting that they might be useful in treating SARS-CoV-2 neuroinvasion, by blocking virus entry [36]. In another study, miR-200 c suppressed ACE2 mRNA and protein expression in rat primary cardiomyocytes and human-induced pluripotent stem cell-derived cardiomyocytes, suggesting a promising strategy to treat SARS-CoV-2 cardiovascular complications [37].…”

Section: Attachment and Entrymentioning

confidence: 99%

MicroRNAs and SARS-CoV-2 life cycle, pathogenesis, and mutations: biomarkers or therapeutic agents?

et al. 2020

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To date, proposed therapies and antiviral drugs have been failed to cure coronavirus disease 2019 (COVID-19) patients. However, at least two drug companies have applied for emergency use authorization with the United States Food and Drug Administration for their coronavirus vaccine candidates and several other vaccines are in various stages of development to determine safety and efficacy. Recently, some studies have shown the role of different human and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) microRNAs (miRNAs) in the pathophysiology of COVID-19. miRNAs are non-coding single-stranded RNAs, which are involved in several physiological and pathological conditions, such as cell proliferation, differentiation, and metabolism. They act as negative regulators of protein synthesis through binding to the 3′ untranslated region (3′ UTR) of the complementary target mRNA, leading to mRNA degradation or inhibition. The databases of Google Scholar, Scopus, PubMed, and Web of Science were searched for literature regarding the importance of miRNAs in the SARS-CoV-2 life cycle, pathogenesis, and genomic mutations. Furthermore, promising miRNAs as a biomarker or antiviral agent in COVID-19 therapy are reviewed.

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Genetic and epigenetic control of ACE2 expression and its possible role in COVID‐19

Lima

Rocha

Moreira

2021

Cell Biochemistry & Function

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Coronavirus disease 2019 (COVID‐19), caused by severe acute respiratory syndrome coronavirus‐2 (SARS‐CoV‐2), is a pandemic that is claiming hundreds of thousands of lives around the world. Angiotensin‐converting enzyme‐2 (ACE2) is a key player in COVID‐19 due to its pivotal role in the SARS‐CoV‐2 infection. This enzyme is expressed throughout the body and the studies conducted so far have shown that its expression varies according to several factors, including cell type, sex, age, disease states and probably SARS‐CoV‐2 infection. Single‐nucleotide polymorphisms (SNPs) and epigenetic mechanisms, including DNA methylation, histone post‐translational modifications and microRNAs, impact ACE2 expression and may explain structural variation. The understanding of how genetic variants and epigenetic markers act to control ACE2 expression in health and disease states may contribute to comprehend several aspects of COVID‐19 that are puzzling researchers and clinicians. This review collects and appraises the literature regarding some aspects in the ACE2 biology, the expression patterns of this molecule, SNPs of the ACE2 gene and epigenetic mechanisms that may impact ACE2 expression in the context of COVID‐19.

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Identification of Novel Hypothalamic MicroRNAs as Promising Therapeutics for SARS-CoV-2 by Regulating ACE2 and TMPRSS2 Expression: An In Silico Analysis

Cited by 35 publications

References 71 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

MicroRNAs and SARS-CoV-2 life cycle, pathogenesis, and mutations: biomarkers or therapeutic agents?

Genetic and epigenetic control of ACE2 expression and its possible role in COVID‐19

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