Exosomal mediated signal transduction through artificial microRNA (amiRNA): A potential target for inhibition of SARS-CoV-2

Vadivalagan, Chithravel; Shitu, Anushka; Kamalakannan, Siva; Chen, Ruei Ming; Serrano‐Aroca, Ángel; Mishra, Vijay; Aljabali, Alaa A. A.; Singh, Sachin Kumar; Chellappan, Dinesh Kumar; Gupta, Gaurav; Dua, Kamal; El‐Tanani, Mohamed; Tambuwala, Murtaza M.; Anand, Krishnan

doi:10.1016/j.cellsig.2022.110334

Cited by 11 publications

(6 citation statements)

References 102 publications

(105 reference statements)

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“…Out of these 10 miRNAs, three of them including hsa-miR-4282, hsa-miR-33a-3p and hsa-miR-4775 were found in several other studies. The hsa-miR-4282 has been shown to target ATF2 gene ( Vadivalagan et al., 2022 ) that arrests the viral infection, hsa-miR-33a-3p targets SMAD4 which is involved in the Wnt signalling pathway ( Yousefi et al., 2020 ), similarly hsa-miR-4775 targets SMAD7 and it plays role in TGF-beta signaling pathway ( Yousefi et al., 2020 ). The hsa-miR-497-3p, inhibits vascular endothelial growth factor A, suppresses angiogenesis, and is found to be involved in the body’s defense mechanisms ( Van Laar et al., 2018 ).…”

Section: Resultsmentioning

confidence: 99%

“…It was observed that some of the predicted miRNAs could target cellular host factors thereby facilitating the replication of SARS-CoV-2. Some of the miRNAs targeting forward genomes of SARS-CoV-2 variants included hsa-miR-3672, hsa-miR-7161-5p, hsa-miR-30b-5p and hsa-miR-3682-5p were have been shown to regulate host factors including ICOSLG, G3BP1/P2, CREB1 respectively ( Vastrad et al., 2020 ; Almutairy et al., 2021 ; Vadivalagan et al., 2022 ). Analysis of reverse sequences of SARS-CoV-2 mutants revealed that has-miR-548 could regulate G3BP1/P2 thereby contributing to viral replication ( Almutairy et al., 2021 ).…”

Section: Resultsmentioning

confidence: 99%

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In silico analysis of SARS-CoV-2 genomes: Insights from SARS encoded non-coding RNAs

Periwal

Bhardwaj

Sarma

et al. 2022

Front. Cell. Infect. Microbiol.

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The recent pandemic caused by Severe Acute Respiratory Syndrome Coronavirus-2 has resulted in enormous deaths around the world. Clues from genomic sequences of parent and their mutants can be obtained to understand the evolving pathogenesis of this virus. Apart from the viral proteins, virus-encoded microRNAs (miRNAs) have been shown to play a vital role in regulating viral pathogenesis. Thus we sought to investigate the miRNAs encoded by SARS-CoV-2, its mutants, and the host. Here, we present the results obtained using a dual approach i.e (i) identifying host-encoded miRNAs that might regulate viral pathogenesis and (ii) identifying viral-encoded miRNAs that might regulate host cell signaling pathways and aid in viral pathogenesis. Analysis utilizing the first approach resulted in the identification of ten host-encoded miRNAs that could target the SARS, SARS-CoV-2, and its mutants. Interestingly our analysis revealed that there is a significantly higher number of host miRNAs that could target the SARS-CoV-2 genome as compared to the SARS reference genome. Results from the second approach resulted in the identification of a set of virus-encoded miRNAs which might regulate host signaling pathways. Our analysis further identified a similar “GA” rich motif in the SARS-CoV-2 and its mutant genomes that was shown to play a vital role in lung pathogenesis during severe SARS infections. In summary, we have identified human and virus-encoded miRNAs that might regulate the pathogenesis of SARS coronaviruses and describe similar non-coding RNA sequences in SARS-CoV-2 that were shown to regulate SARS-induced lung pathology in mice.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

In silico analysis of SARS-CoV-2 genomes: Insights from SARS encoded non-coding RNAs

Periwal

Bhardwaj

Sarma

et al. 2022

Front. Cell. Infect. Microbiol.

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show abstract

“…The highly correlated expression of RGS2 with CXCL8, PTGS2, NAMPT, ILB1 and further inflammatory genes in COVID-19 positive nasopharyngeal swabs ( Figures 1-5, Table 1 ) suggests the involvement of a common regulator, which might explain the distinct classes of COVID-19 symptoms. Changes in the expression of circulating or exosomal microRNAs in COVID-19 is one factor that might explain at least some of the observed gene expression alterations (26, 27). Further studies of COVID-19 animal models are required for clarifying the cellular mechanisms by which SARS-CoV-2 infection drives this differential expression.…”

Section: Discussionmentioning

confidence: 99%

Elevated expression of RGS2 may underlie reduced olfaction in COVID-19 patients

Avnat

Shapira

Genevieve

et al. 2022

Preprint

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Anosmia is common in COVID-19 patients, lasting for weeks or months following recovery. The biological mechanism underlying olfactory deficiency in COVID-19 does not involve direct damage to nasal olfactory neurons, which do not express the proteins required for SARS-CoV-2 infection. A recent study suggested that anosmia results from downregulation of olfactory receptors. We hypothesized that anosmia in COVID-19 may also reflect SARS-CoV-2 infection-driven elevated expression of regulator of G protein signaling 2 (RGS2), a key regulator odorant receptor, thereby silencing their signaling. To test our hypothesis, we analyzed gene expression of nasopharyngeal swabs from SARS-CoV-2 positive patients and non-infected controls (two published RNA-sequencing datasets, 580 individuals). Our analysis found upregulated RGS2 expression in SARS-CoV-2 positive patients (FC=14.5, Padj=1.69e-05 and FC=2.4; Padj=0.001, per dataset). Additionally, RGS2 expression was strongly correlated with PTGS2, IL1B, CXCL8, NAMPT and other inflammation markers with substantial upregulation in early infection. These observations suggest that upregulated expression of RGS2 may underlie anosmia in COVID-19 patients. As a regulator of numerous G-protein coupled receptors, RGS2 may drive further neurological symptoms of COVID-19. Studies are required for clarifying the cellular mechanisms by which SARS-CoV-2 infection drives the upregulation of RGS2 and other genes implicated in inflammation. Insights on these pathways may assist in understanding anosmia and additional neurological symptoms reported in COVID-19 patients.

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“…The spectrum of possible viral interference might also involve intracellular transport mechanisms and cell-cell communications. Many of these "actions" have a deep impact on human biology and inter-organ signaling, according to recent research on the effects of COVID-19 on the human organism [55,56]. In particular, we relate the most significant one to signaling by receptor tyrosine kinases (RTKs), a family of proteins that act as cell surface receptors for various factors, such as cytokines and hormones.…”

Section: Quantitative Evaluation Of the Biological Functionalities In...mentioning

confidence: 99%

A Tiny Viral Protein, SARS-CoV-2-ORF7b: Functional Molecular Mechanisms

Mansueto,

Fusco,

Colonna

2024

Biomolecules

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This study presents the interaction with the human host metabolism of SARS-CoV-2 ORF7b protein (43 aa), using a protein–protein interaction network analysis. After pruning, we selected from BioGRID the 51 most significant proteins among 2753 proven interactions and 1708 interactors specific to ORF7b. We used these proteins as functional seeds, and we obtained a significant network of 551 nodes via STRING. We performed topological analysis and calculated topological distributions by Cytoscape. By following a hub-and-spoke network architectural model, we were able to identify seven proteins that ranked high as hubs and an additional seven as bottlenecks. Through this interaction model, we identified significant GO-processes (5057 terms in 15 categories) induced in human metabolism by ORF7b. We discovered high statistical significance processes of dysregulated molecular cell mechanisms caused by acting ORF7b. We detected disease-related human proteins and their involvement in metabolic roles, how they relate in a distorted way to signaling and/or functional systems, in particular intra- and inter-cellular signaling systems, and the molecular mechanisms that supervise programmed cell death, with mechanisms similar to that of cancer metastasis diffusion. A cluster analysis showed 10 compact and significant functional clusters, where two of them overlap in a Giant Connected Component core of 206 total nodes. These two clusters contain most of the high-rank nodes. ORF7b acts through these two clusters, inducing most of the metabolic dysregulation. We conducted a co-regulation and transcriptional analysis by hub and bottleneck proteins. This analysis allowed us to define the transcription factors and miRNAs that control the high-ranking proteins and the dysregulated processes within the limits of the poor knowledge that these sectors still impose.

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Exosomal mediated signal transduction through artificial microRNA (amiRNA): A potential target for inhibition of SARS-CoV-2

Cited by 11 publications

References 102 publications

In silico analysis of SARS-CoV-2 genomes: Insights from SARS encoded non-coding RNAs

In silico analysis of SARS-CoV-2 genomes: Insights from SARS encoded non-coding RNAs

Elevated expression of RGS2 may underlie reduced olfaction in COVID-19 patients

A Tiny Viral Protein, SARS-CoV-2-ORF7b: Functional Molecular Mechanisms

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