miRNAs; a novel strategy for the treatment of COVID‐19

Cell Biology International, Год журнала: 2021, Номер 45(10), С. 2045 - 2053

Опубликована: Июнь 28, 2021

Abstract Coronavirus disease 2019 (COVID‐19) is the seventh member of bat severe acute respiratory syndrome family. COVID‐19 can fuse their envelopes with host cell membranes and deliver genetic material. attacks system stimulates inflammatory responses, enhances recruitment immune cells, promotes angiotensin‐converting enzyme 2 activities. Patients confirmed may have experienced fever, dry cough, headache, dyspnea, kidney injury, distress syndrome, heart injury. Several strategies such as oxygen therapy, ventilation, antibiotic or antiviral renal replacement therapy are commonly used to decrease COVID‐19‐associated mortality. However, these approaches not be good treatment options. Therefore, search for an alternative‐novel urgently important prevent progression. Recently, microRNAs (miRNAs) emerged a promising strategy COVID‐19. The design oligonucleotide against material might suppress virus RNA translation. previous studies shown that miRNAs play role improve patients by binding 3′‐untranslated region (UTR) 5′‐UTR viral in COVID‐19‐host interplay replication. interact multiple pathways reduce biomarkers, thrombi formation, tissue damage accelerate patient outcome. information this review provides summary current clinical application treatments

Язык: Английский

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Epigenetic underpinnings of inflammation: Connecting the dots between pulmonary diseases, lung cancer and COVID-19

Seminars in Cancer Biology, Год журнала: 2021, Номер 83, С. 384 - 398

Опубликована: Янв. 20, 2021

Язык: Английский

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Cellular miR-150-5p may have a crucial role to play in the biology of SARS-CoV-2 infection by regulating nsp10 gene

RNA Biology, Год журнала: 2021, Номер 19(1), С. 1 - 11

Опубликована: Дек. 14, 2021

The role for circulating miRNAs as biomarkers of the COVID-19 disease remains uncertain. We analysed miRNA profile in twelve patients with moderate-severe disease. This analysis was conducted by performing next generation sequencing (NGS) followed real-time polymerase chain reaction (RT-qPCR). Compared healthy controls, we detected significant changes patients. that were significantly altered all miR-150-5p, miR-375, miR-122-5p, miR-494-3p, miR-3197, miR-4690-5p, miR-1915-3p, and miR-3652. Infection assays performed using mimics HEK-293 T cells determined miR-150-5p to have a crucial SARS-CoV-2 infection this based on following data: (i) mimic lowered vitro infection; (ii) inhibitor reversed effects cells; (iii) novel recognition element (MRE) identified coding strand nsp10, expression which could be inhibited mimic. Our findings footprints A combination co-transfection Western blotting experiments also ability inhibit via directly interacting MRE nsp10. investigation showed sharp decline plasma levels may support enhanced infection. Furthermore, study provides insight into one possible mechanism COVID-19-induced promote modulating nsp10 expression.

Язык: Английский

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MiRNA-SARS-CoV-2 dialogue and prospective anti-COVID-19 therapies

Life Sciences, Год журнала: 2022, Номер 305, С. 120761 - 120761

Опубликована: Июль 2, 2022

Язык: Английский

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MicroRNAs: Small but Key Players in Viral Infections and Immune Responses to Viral Pathogens

Biology, Год журнала: 2023, Номер 12(10), С. 1334 - 1334

Опубликована: Окт. 14, 2023

Since the discovery of microRNAs (miRNAs) in C. elegans 1993, field miRNA research has grown steeply. These single-stranded non-coding RNA molecules canonically work at post-transcriptional phase to regulate protein expression. miRNAs are known viral infection and ensuing host immune response. Evolving suggests assets investigation therapeutics diagnostics. In this review, we succinctly summarize latest findings (i) mechanisms underpinning regulation infection, (ii) response pathogens, (iii) miRNA-based diagnostics targeting pathogens challenges, (iv) patents market landscape. Our show differential expression may serve as a prognostic biomarker for infections regard predicting severity or adverse health effects associated with diseases. While there is huge potential technology, novel approach using mimics enhance antiviral activity antagonists inhibit pro-viral been an ongoing endeavor. Significant hurdles remain terms delivery, stability, efficacy, safety/tolerability, specificity. Addressing these challenges pave path harnessing full modern medicine.

Язык: Английский

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ACE2 Nascence, trafficking, and SARS-CoV-2 pathogenesis: the saga continues

Human Genomics, Год журнала: 2021, Номер 15(1)

Опубликована: Янв. 29, 2021

With the emergence of novel coronavirus SARS-CoV-2 since December 2019, more than 65 million cases have been reported worldwide. This virus has shown high infectivity and severe symptoms in some cases, leading to over 1.5 deaths globally. Despite collaborative concerted research efforts that made, no effective medication for COVID-19 (coronavirus disease-2019) is currently available. uses angiotensin-converting enzyme 2 (ACE2) as an initial mediator viral attachment host cell invasion. ACE2 widely distributed human tissues including surface lung cells which represent primary site infection. Inhibiting or reducing availability represents a promising therapy tackling COVID-19. In this context, most ACE2-based therapeutic strategies aimed tackle through use (ACE) inhibitors neutralizing by exogenous administration ACE2, does not directly aim reduce its membrane availability. However, review, we present different perspective focusing on subcellular localization trafficking ACE2. Membrane targeting shedding cellular pathways internalization are well elucidated literature. Therefore, hereby overview fate newly synthesized post translational modifications, what known pathways. addition, highlight possibility identified missense variants might affect efficiency hence may explain observed variable severity infections. Moreover, extensive understanding these processes necessarily required evaluate potential credible target.

Язык: Английский

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Human MicroRNAs Interacting With SARS-CoV-2 RNA Sequences: Computational Analysis and Experimental Target Validation

Frontiers in Genetics, Год журнала: 2021, Номер 12

Опубликована: Июнь 7, 2021

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a novel RNA virus affecting humans, causing form of pulmonary disorder named COVID-19, declared pandemic by the World Health Organization. MicroRNAs (miRNA) play an emerging and important role in interplay between viruses host cells. Although impact miRNAs on SARS-CoV-2 infection has been predicted, experimental data are still missing. This study started bioinformatics prediction cellular potentially targeting viral RNAs; then, number criteria also based evidence biology were applied, giving rise to eight promising binding miRNAs. Their interaction with sequences was experimentally validated transfecting luciferase-based reporter plasmids carrying target or their inverted into lung A549 cell line. Transfection resulted reduction luciferase activity for five out potential sites, suggesting responsiveness endogenously expressed Co-transfection along miRNA mimics led further strong activity, validating miR-219a-2-3p, miR-30c-5p, miR-378d, miR-29a-3p, miR-15b-5p, sequences. miR-15b able repress plasmid-driven Spike expression. Intriguingly, fully conserved more recent variants such as United Kingdom variant B.1.1.7 South Africa 501Y.V2. Overall, this provides first specific sequences, thus contributing understanding molecular mechanisms underlying pathogenesis envisage innovative therapeutic interventions diagnostic tools.

Язык: Английский

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SnoRNAs and miRNAs Networks Underlying COVID-19 Disease Severity

Vaccines, Год журнала: 2021, Номер 9(10), С. 1056 - 1056

Опубликована: Сен. 23, 2021

There is a lack of predictive markers for early and rapid identification disease progression in COVID-19 patients. Our study aims at identifying microRNAs (miRNAs)/small nucleolar RNAs (snoRNAs) as potential biomarkers severity. Using differential expression analysis microarray data (n = 29), we identified hsa-miR-1246, ACA40, hsa-miR-4532, hsa-miR-145-5p, ACA18 the top five differentially expressed transcripts severe versus asymptomatic, hsa-miR-3609, ENSG00000212378 (SNORD78), hsa-miR-1231, hsa-miR-885-3p most significant mild cases. Moreover, found that white blood cell (WBC) count, absolute neutrophil count (ANC), (%), lymphocyte red (RBC) hemoglobin, hematocrit, D-Dimer, albumin are significantly correlated with miRNAs snoRNAs. We report unique miRNA snoRNA profile associated higher risk severity cohort SARS-CoV-2 infected Altogether, present COVID-19-associated microRNA (miRNA)/small RNA (snoRNA) signature, highlighting their importance infection.

Язык: Английский

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Bronchial Aspirate-Based Profiling Identifies MicroRNA Signatures Associated With COVID-19 and Fatal Disease in Critically Ill Patients

Frontiers in Medicine, Год журнала: 2022, Номер 8

Опубликована: Фев. 3, 2022

The pathophysiology of COVID-19-related critical illness is not completely understood. Here, we analyzed the microRNA (miRNA) profile bronchial aspirate (BAS) samples from COVID-19 and non-COVID-19 patients admitted to ICU identify prognostic biomarkers fatal outcomes define molecular pathways involved in disease adverse events.Two patient populations were included (n = 89): (i) a study population composed critically ill patients; (ii) prospective cohort survivors non-survivors among assisted by invasive mechanical ventilation (IMV). BAS obtained bronchoaspiration during stay. miRNA was using RT-qPCR. Detailed biomarker bioinformatics analyses performed.The deregulation five ratios (miR-122-5p/miR-199a-5p, miR-125a-5p/miR-133a-3p, miR-155-5p/miR-486-5p, miR-214-3p/miR-222-3p, miR-221-3p/miR-27a-3p) observed when compared. In addition, segregated between nonsurvivors (miR-1-3p/miR-124-3p, miR-125b-5p/miR-34a-5p, miR-126-3p/miR-16-5p, miR-199a-5p/miR-9-5p, miR-221-3p/miR-491-5p). Through multivariable analysis, constructed ratio-based prediction model for mortality that optimized best combination (miR-125b-5p/miR-34a-5p, (AUC 0.85) miR-199a-5p/miR-9-5p ratio 0.80) showed an optimal discrimination value outperformed clinical predictor (days first symptoms IMV initiation, AUC 0.73). survival analysis confirmed usefulness individual at high risk following initiation. Functional enrichment identified pathological mechanisms implicated fibrosis, coagulation, viral infections, immune responses inflammation.COVID-19 induces specific signature patients. hold collective potential improve risk-based stratification initiation illness. biological role host profiles may allow better understanding different axes disease.

Язык: Английский

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Competing endogenous RNA network mediated by circ_3205 in SARS-CoV-2 infected cells

Cellular and Molecular Life Sciences, Год журнала: 2022, Номер 79(2)

Опубликована: Янв. 17, 2022

Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) is a new member of the Betacoronaviridae family, responsible for recent pandemic outbreak COVID-19. To start exploring molecular events that follow host cell infection, we queried VirusCircBase and identified circular RNA (circRNA) predicted to be synthesized by SARS-CoV-2, circ_3205, which used probe: (i) training cohort comprised two pools cells from three nasopharyngeal swabs SARS-CoV-2 infected (positive) or uninfected (negative, UCs) individuals; (ii) validation made up 12 positive 3 negative samples. The expression circRNAs, miRNAs miRNA targets was assayed through real-time PCR. CircRNA-miRNA interactions were TarpMiR, Analysis Common Targets RNAs (ACT), STarMir tools. Enrichment biological processes list retrieved DIANA miRPath v3.0. Our results showed circ_3205 expressed only in samples its amount positively correlated with Spike (S) mRNA viral load (r values = 0.80952 0.84867, Spearman's correlation test, respectively). Human (hsa) miR-298 interact all predictive KCNMB4 PRKCE as hsa-miR-298 targets. Interestingly, function both blood coagulation immune response. mRNAs upregulated compared UCs (6 8.1-fold, p 0.049 0.02, Student's t respectively) their 0.6 0.25, We propose our convincingly suggest circRNA upon infection it may behave competitive endogenous (ceRNA), sponging contributing upregulation mRNAs.

Язык: Английский

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