COVID-19 Virulence in Aged Patients Might Be Impacted by the Host Cellular MicroRNAs Abundance/Profile

Fulzele, Sadanand; Sahay, Bikash; Yusufu, Ibrahim; Lee, Tae Jin; Sharma, Ashok; Kolhe, Ravindra; Isales, Carlos M.

doi:10.14336/ad.2020.0428

Cited by 111 publications

(158 citation statements)

References 49 publications

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“…As one can expect, viruses with high genomic similarity such as SARS-CoV-2/SARS-CoV or HCoV-229E/HCoV-NL63 had higher number of shared binding sites. Similar computational approach to discover direct miRNA-virus interactions was already employed by Fulzele et al (2020) . Namely, using miRDB researchers predicted miRNAs targeting RNAs of SARS-CoV-2 and SARS-CoV.…”

Section: Discussionmentioning

confidence: 99%

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Potential role of cellular miRNAs in coronavirus-host interplay

Nersisyan

Engibaryan

Gorbonos

et al. 2020

PeerJ

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Host miRNAs are known as important regulators of virus replication and pathogenesis. They can interact with various viruses through several possible mechanisms including direct binding of viral RNA. Identification of human miRNAs involved in coronavirus-host interplay becomes important due to the ongoing COVID-19 pandemic. In this article we performed computational prediction of high-confidence direct interactions between miRNAs and seven human coronavirus RNAs. As a result, we identified six miRNAs (miR-21-3p, miR-195-5p, miR-16-5p, miR-3065-5p, miR-424-5p and miR-421) with high binding probability across all analyzed viruses. Further bioinformatic analysis of binding sites revealed high conservativity of miRNA binding regions within RNAs of human coronaviruses and their strains. In order to discover the entire miRNA-virus interplay we further analyzed lungs miRNome of SARS-CoV infected mice using publicly available miRNA sequencing data. We found that miRNA miR-21-3p has the largest probability of binding the human coronavirus RNAs and being dramatically up-regulated in mouse lungs during infection induced by SARS-CoV.

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Section: Discussionmentioning

confidence: 99%

“…In a recent article, Fulzele et al (2020) found hundreds of miRNAs which can potentially bind to SARS-CoV-2 RNA as well as the RNA of the highly similar SARS-CoV coronavirus. However, this large miRNA list should be narrowed to find high-confidence interactions which should be further experimentally validated.…”

Section: Introductionmentioning

confidence: 99%

Potential role of cellular miRNAs in coronavirus-host interplay

Nersisyan

Engibaryan

Gorbonos

et al. 2020

PeerJ

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show abstract

“…In silico analysis shows that SARS-CoV-2 may be targeted by over 800 human microRNAs (miRs); circa 65% of which target the related SARS-CoV, but over 300 miRs are unique in comparison. This change in the affected ncRNA network may lead to the different clinical manifestations and infectivity which are apparent in the current pandemic ( 36 ). Since lncRNAs form a complex infection-associated activity profile and may operate as “sponges” modulating miR regulatory activities and response to infection ( 37 – 39 ), we expected changes in the levels of such ncRNAs to relate to the pathogenesis and hyper-inflammatory nature of COVID-19 ( 12 , 40 ) as well as to its predicted risk of neurologic sequelae ( 24 , 41 – 43 ).…”

Section: Introductionmentioning

confidence: 99%

The Neat Dance of COVID-19: NEAT1, DANCR, and Co-Modulated Cholinergic RNAs Link to Inflammation

2020

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The COVID-19 pandemic exerts inflammation-related parasympathetic complications and post-infection manifestations with major inter-individual variability. To seek the corresponding transcriptomic origins for the impact of COVID-19 infection and its aftermath consequences, we sought the relevance of long and short non-coding RNAs (ncRNAs) for susceptibility to COVID-19 infection. We selected inflammation-prone men and women of diverse ages among the cohort of Genome Tissue expression (GTEx) by mining RNA-seq datasets from their lung, and blood tissues, followed by quantitative qRT-PCR, bioinformatics-based network analyses and thorough statistics compared to brain cell culture and infection tests with COVID-19 and H1N1 viruses. In lung tissues from 57 inflammation-prone, but not other GTEx donors, we discovered sharp declines of the lung pathology-associated ncRNA DANCR and the nuclear paraspeckles forming neuroprotective ncRNA NEAT1. Accompanying increases in the acetylcholine-regulating transcripts capable of controlling inflammation co-appeared in SARS-CoV-2 infected but not H1N1 influenza infected lung cells. The lung cells-characteristic DANCR and NEAT1 association with inflammation-controlling transcripts could not be observed in blood cells, weakened with age and presented sex-dependent links in GTEx lung RNA-seq dataset. Supporting active involvement in the inflammatory risks accompanying COVID-19, DANCR’s decline associated with decrease of the COVID-19-related cellular transcript ACE2 and with sex-related increases in coding transcripts potentiating acetylcholine signaling. Furthermore, transcription factors (TFs) in lung, brain and cultured infected cells created networks with the candidate transcripts, indicating tissue-specific expression patterns. Supporting links of post-infection inflammatory and cognitive damages with cholinergic mal-functioning, man and woman-originated cultured cholinergic neurons presented differentiation-related increases of DANCR and NEAT1 targeting microRNAs. Briefly, changes in ncRNAs and TFs from inflammation-prone human lung tissues, SARS-CoV-2-infected lung cells and man and woman-derived differentiated cholinergic neurons reflected the inflammatory pathobiology related to COVID-19. By shifting ncRNA differences into comparative diagnostic and therapeutic profiles, our RNA-sequencing based Resource can identify ncRNA regulating candidates for COVID-19 and its associated immediate and predicted long-term inflammation and neurological complications, and sex-related therapeutics thereof. Our findings encourage diagnostics of involved tissue, and further investigation of NEAT1-inducing statins and anti-cholinergic medications in the COVID-19 context.

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“…In recent work, Fulzele with co-authors found hundreds of miRNAs which can potentially bind to the SARS-CoV-2 RNA as well as the RNA of the highly similar SARS-CoV coronavirus (Fulzele et al, 2020). However, this large miRNA list should be narrowed to find high-confidence interactions which should be further experimentally validated.…”

Section: /15mentioning

confidence: 99%

The potential role of miR-21-3p in coronavirus-host interplay

Nersisyan

Engibaryan

Gorbonos

et al. 2020

Preprint

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ABSTRACTHost miRNAs are known as important regulators of virus replication and pathogenesis. They can interact with various viruses by several possible mechanisms including direct binding the viral RNA. Identification of human miRNAs involved in coronavirus-host interplay is becoming important due to the ongoing COVID-19 pandemic. In this work we performed computational prediction of high-confidence direct interactions between miRNAs and seven human coronavirus RNAs. In order to uncover the entire miRNA-virus interplay we further analyzed lungs miRNome of SARS-CoV infected mice using publicly available miRNA sequencing data. We found that miRNA miR-21-3p has the largest probability of binding the human coronavirus RNAs and being dramatically up-regulated in mouse lungs during infection induced by SARS-CoV. Further bioinformatic analysis of binding sites revealed high conservativity of miR-21-3p binding regions within RNAs of human coronaviruses and their strains.

show abstract

COVID-19 Virulence in Aged Patients Might Be Impacted by the Host Cellular MicroRNAs Abundance/Profile

Cited by 111 publications

References 49 publications

Potential role of cellular miRNAs in coronavirus-host interplay

Potential role of cellular miRNAs in coronavirus-host interplay

The Neat Dance of COVID-19: NEAT1, DANCR, and Co-Modulated Cholinergic RNAs Link to Inflammation

The potential role of miR-21-3p in coronavirus-host interplay

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