A computational and bioinformatic analysis of ACE2: an elucidation of its dual role in COVID-19 pathology and finding its associated partners as potential therapeutic targets

Khan, Abeedha Tu Allah; Khalid, Zumama; Zahid, Hafsa; Yousaf, Muhammad; Shakoori, A. R.

doi:10.1080/07391102.2020.1833760

Cited by 20 publications

(16 citation statements)

References 76 publications

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“… Pakistan To provide a computational and bioinformatics-based analysis of ACE2 and its corresponding regulatory miRNAs, elucidating its role in the COVID-19 pathogenesis. ( Khan et al, 2020a ) 24 Lu D August 30, 2020. Germany To identify miRNAs predicted to regulate ACE2 using an in-silico approach.…”

Section: Resultsmentioning

confidence: 99%

“… Targets both SARS-CoV-2 and SARS isolates miR-16-2-3p Not reported Upregulation on SARS-CoV-2 infected samples Chow and Salmena, 2020 , Li et al, 2020 . miR-1246 ACE2 Upregulation associated with Acute Respiratory Distress Syndrome (ARDS) Khan et al, 2020a , Zhang et al, 2020 . Downregulation in the small airway epithelium of smokers compared to non-smokers Targets the 3’UTR sequence of ACE2 mRNA miR-200c-3p ACE2 Induced overexpression resulted in downregulation of ACE2 in human cardiomyocytes.…”

Section: Resultsmentioning

confidence: 99%

“…As expected, miRNAs that target ACE2 and TMPRSS2 can regulate their expression and function. 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: 99%

Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

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

View full text Add to dashboard Cite

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“…SARS-CoV-1 S-protein binding to ACE2 was shown to downregulate expression of ACE2 in vitro and in vivo [ 109 , 110 ]. ACE2 downregulation is associated with poor prognosis in SARS and COVID-19 patients, by exacerbating ARDS [ 111 , 112 , 113 ], severe pneumonia [ 110 , 112 ], and extra-pulmonary conditions including acute kidney injury and cardiac injury [ 111 , 112 ]. Lung failure due to injection of SARS-CoV-1 S-protein into mice could be partially reversed by blocking the RAAS in vivo [ 110 ].…”

Section: Cellular Ace2 Downregulation Leading To Endothelial Dysfumentioning

confidence: 99%

Endothelium Infection and Dysregulation by SARS-CoV-2: Evidence and Caveats in COVID-19

Bernard

Limonta

Mahal

et al. 2020

Viruses

152

130

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The ongoing pandemic of coronavirus disease 2019 (COVID-19) caused by the acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) poses a persistent threat to global public health. Although primarily a respiratory illness, extrapulmonary manifestations of COVID-19 include gastrointestinal, cardiovascular, renal and neurological diseases. Recent studies suggest that dysfunction of the endothelium during COVID-19 may exacerbate these deleterious events by inciting inflammatory and microvascular thrombotic processes. Although controversial, there is evidence that SARS-CoV-2 may infect endothelial cells by binding to the angiotensin-converting enzyme 2 (ACE2) cellular receptor using the viral Spike protein. In this review, we explore current insights into the relationship between SARS-CoV-2 infection, endothelial dysfunction due to ACE2 downregulation, and deleterious pulmonary and extra-pulmonary immunothrombotic complications in severe COVID-19. We also discuss preclinical and clinical development of therapeutic agents targeting SARS-CoV-2-mediated endothelial dysfunction. Finally, we present evidence of SARS-CoV-2 replication in primary human lung and cardiac microvascular endothelial cells. Accordingly, in striving to understand the parameters that lead to severe disease in COVID-19 patients, it is important to consider how direct infection of endothelial cells by SARS-CoV-2 may contribute to this process.

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“…Moreover, several studies have investigated host miRNAs that directly target the expression of ACE2 and TMPRSS2, which are critical for viral entry and insertion. For example, miR-1246, miR-200c-3p, and miR-125a-5p were predicted to regulate ACE2 expression levels and their associated pathways [ 54 - 56 ], while let-7a-5p and let-7d-5p were reported to negatively correlate with TMPRSS2 expression [ 56 - 58 ]. These results demonstrate the impact of host cellular miRNAs on SARS-CoV-2 infection and COVID-19 pathogenesis.…”

Section: Methodsmentioning

confidence: 99%

Interplays between human microbiota and microRNAs in COVID-19 pathogenesis: a literature review

Hong

Kim

2021

Phys Act Nutr

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[Purpose] Recent studies have shown that COVID-19 is often associated with altered gut microbiota composition and reflects disease severity. Furthermore, various reports suggest that the interaction between COVID-19 and host-microbiota homeostasis is mediated through the modulation of microRNAs (miRNAs). Thus, in this review, we aim to summarize the association between human microbiota and miRNAs in COVID-19 pathogenesis.[Methods] We searched for the existing literature using the keywords such “COVID-19 or microbiota,” “microbiota or microRNA,” and “COVID-19 or probiotics” in PubMed until March 31, 2021. Subsequently, we thoroughly reviewed the articles related to microbiota and miRNAs in COVID-19 to generate a comprehensive picture depicting the association between human microbiota and microRNAs in the pathogenesis of COVID-19.[Results] There exists strong experimental evidence suggesting that the composition and diversity of human microbiota are altered in COVID-19 patients, implicating a bidirectional association between the respiratory and gastrointestinal tracts. In addition, SARS-CoV-2 encoded miRNAs and host cellular microRNAs modulated by human microbiota can interfere with viral replication and regulate host gene expression involved in the initiation and progression of COVID-19. These findings suggest that the manipulation of human microbiota with probiotics may play a significant role against SARS-CoV-2 infection by enhancing the host immune system and lowering the inflammatory status.[Conclusion] The human microbiota-miRNA axis can be used as a therapeutic approach for COVID-19. Hence, further studies are needed to investigate the exact molecular mechanisms underlying the regulation of miRNA expression in human microbiota and how these miRNA profiles mediate viral infection through host-microbe interactions.

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A computational and bioinformatic analysis of ACE2: an elucidation of its dual role in COVID-19 pathology and finding its associated partners as potential therapeutic targets

Cited by 20 publications

References 76 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

Endothelium Infection and Dysregulation by SARS-CoV-2: Evidence and Caveats in COVID-19

Interplays between human microbiota and microRNAs in COVID-19 pathogenesis: a literature review

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