MicroRNAs Bioinformatics Analyses Identifying HDAC Pathway as a Putative Target for Existing Anti‐COVID‐19 Therapeutics

Frontiers in Pharmacology, Год журнала: 2020, Номер 11

Опубликована: Дек. 8, 2020

Over 313,000 SARS-CoV-2 positive cases have been confirmed in Italy as of 30 September 2020, and the number deaths exceeding thirty-five thousand makes among list most significantly affected countries world. Such an enormous occurrence infections death raises urgent demand for effective available treatments. Discovering cellular/molecular mechanisms pathogenicity is paramount importance to understand how infection becomes a disease plan any therapeutic approach. In this regard, we performed silico analysis predict putative virus targets evidence already therapeutics. Literature experimental results identified angiotensin-converting enzyme ACE Spike proteins particularly involved COVID-19. Consequently, investigated signalling pathways modulated by two through query miRNet, platform linking miRNAs, targets, functions. Our bioinformatics predicted microRNAs (miRs), miR-335-5p miR-26b-5p, being together with histone deacetylate (HDAC) pathway. Notably, our ACE/ACE2-ATR1-Cholesterol-HDAC axis signals that also matched some clinical data. We hypothesize current EMA-approved, off-label HDAC inhibitors (HDACis) drugs may be repurposed limit or block host-virus interactions. Moreover, ranked compounds provided further evaluation safety, efficacy, effectiveness.

Язык: Английский

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Immunogenetic Association Underlying Severe COVID-19

Vaccines, Год журнала: 2020, Номер 8(4), С. 700 - 700

Опубликована: Ноя. 20, 2020

SARS-CoV2 has caused the current pandemic of new coronavirus disease 2019 (COVID-19) worldwide. Clinical outcomes COVID-19 illness range broadly from asymptotic and mild to a life-threatening situation. This casts uncertainties for defining host determinants underlying severity. Recent genetic analyses based on extensive clinical sample cohorts using genome-wide association studies (GWAS) high throughput sequencing curation revealed errors gene loci associated with about 20% cases. Significantly, most these critical are enriched in two immune signaling pathways, i.e., interferon-mediated antiviral chemokine-mediated/inflammatory signaling. In line profiling studies, broad spectrum could be explained by immuno-pathological regulation immunogenetic pathways through various epigenetic mechanisms, which further interconnect other vital components such as those renin–angiotensin–aldosterone system (RAAS) because its direct interaction virus causing COVID-19. Together, key genes unraveled may provide targets precisely early risk diagnosis prophylactic design relieve severe The confounding mechanisms understanding broadness illness.

Язык: Английский

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SARS-CoV-2 and the Nucleus

International Journal of Biological Sciences, Год журнала: 2022, Номер 18(12), С. 4731 - 4743

Опубликована: Янв. 1, 2022

The ongoing COVID-19 pandemic is caused by an RNA virus, SARS-CoV-2.The genome of SARS-CoV-2 lacks a nuclear phase in its life cycle and replicated the cytoplasm.However, interfering with trafficking using pharmacological inhibitors greatly reduces virus infection replication other coronaviruses blocked enucleated cells, suggesting critical role nucleus infection.Here, we summarize alternations pathways SARS-CoV-2, including translocation pathways, innate immune responses, mRNA metabolism, epigenetic mechanisms, DNA damage response, cytoskeleton regulation, rupture.We consider how these contribute to discuss therapeutic treatments that target focusing on small molecule drugs are being used clinical studies.

Язык: Английский

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Understanding the epigenetic mechanisms in SARS CoV-2 infection and potential therapeutic approaches

Virus Research, Год журнала: 2022, Номер 318, С. 198853 - 198853

Опубликована: Июнь 28, 2022

Язык: Английский

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Deciphering epigenetic(s) role in modulating susceptibility to and severity of COVID-19 infection and/or outcome: a systematic rapid review

Environmental Science and Pollution Research, Год журнала: 2021, Номер 28(39), С. 54209 - 54221

Опубликована: Авг. 12, 2021

COVID-19 pandemic waves hitting worldwide result in drastic postinfection complications with interindividual variations, which raised the question for cause of these observed variations. This urged to think "the impact environment-affected genes"? In an attempt unravel genes, a systematic rapid review was conducted study host or viral epigenetic modulation on infection susceptibility and/or outcome." Electronic databases including Web Science, SCOPUS, Cochrane Central Register Controlled Trials, PubMed, and Google Scholar, other were searched. The search strings included "COVID-19" OR "SARS-CoV-2" AND (Epigenetics'). Articles randomized clinical trials (RCTs) observational designs, humans available English language, selected, respect "The interplay between SARS-CoV-2 virus Epigenetics" published from 2020 February 2021 (but not limited 2020, being expanded 2015). Database yielded 1330 articles; after screening, exclusion, further filtrations, 51 articles included. Susceptibility is related viral-microRNAs (miRNAs) alter virulence transmitted strains host-miRNA-related innate immunity. Host-DNA methylation chromatin remodeling may be implicated severe cytokine storm that can ultimately results fatal outcome.

Язык: Английский

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Management of COVID-19 in patients with seizures: Mechanisms of action of potential COVID-19 drug treatments and consideration for potential drug-drug interactions with anti-seizure medications

Epilepsy Research, Год журнала: 2021, Номер 174, С. 106675 - 106675

Опубликована: Май 19, 2021

Язык: Английский

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Factors regulating dynamics of angiotensin-converting enzyme-2 (ACE2), the gateway of SARS-CoV-2: Epigenetic modifications and therapeutic interventions by epidrugs

Biomedicine & Pharmacotherapy, Год журнала: 2021, Номер 143, С. 112095 - 112095

Опубликована: Авг. 30, 2021

Angiotensin-converting enzyme-2 (ACE2) is one of the major components renin-angiotensin system (RAS) and participates in physiological functions cardiovascular lungs. Recent studies identified ACE2 as receptor for S-protein novel severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) thus acts gateway viral entry into human body. Virus infection causes an imbalance RAS axis induces lungs injury fibrosis. Various factors regulate expression patterns well control its epigenetic status at both transcription translational levels. This review mainly focused on impact environmental toxicants, drugs, endocrine disruptors, hypoxia controlling parameters possible modulation by changes which are marked DNA methylation, histone modifications, micro-RNAs (miRNAs) profile. Furthermore, we have emphasized interventions various phytochemicals bioactive compounds epidrugs that ACE2-S-protein interaction thereby curb infection. Since important component RAAS a crucial point SARS-CoV-2, dynamics response to extrinsic intrinsic contemporary relevance. We collated updated information modulated epidrugs, urge take over further these regulators unravel many more systemic linkages related metabolic infectious diseases, general SARS-CoV-2 particular development targeted interventions.

Язык: Английский

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SARS-CoV-2: An Overview of the Genetic Profile and Vaccine Effectiveness of the Five Variants of Concern

Pathogens, Год журнала: 2022, Номер 11(5), С. 516 - 516

Опубликована: Апрель 26, 2022

With the onset of COVID-19 pandemic, enormous efforts have been made to understand genus SARS-CoV-2. Due high rate global transmission, mutations in viral genome were inevitable. A full understanding and its possible changes represents one crucial aspects pandemic management. Structural protein S plays an important role pathogenicity SARS-CoV-2, occurring at this level leading forms with increased affinity for ACE2 receptors, higher transmissibility infectivity, resistance neutralizing antibodies immune escape, increasing risk infection disease severity. Thus, five variants concern are currently being discussed, Alpha, Beta, Gamma, Delta Omicron. In present review, a comprehensive summary following critical regarding SARS-CoV-2 has made: (i) genomic characteristics SARS-CoV-2; (ii) pathological mechanism penetration into cell action on specific receptors; (iii) genome; (iv) implications diagnosis, treatment, vaccination.

Язык: Английский

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The role of DNA methylation in personalized medicine for immune-related diseases

Pharmacology & Therapeutics, Год журнала: 2023, Номер 250, С. 108508 - 108508

Опубликована: Авг. 9, 2023

Язык: Английский

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Hospital mortality in COVID-19 patients in Belgium treated with statins, ACE inhibitors and/or ARBs

Human Vaccines & Immunotherapeutics, Год журнала: 2021, Номер 17(9), С. 2841 - 2850

Опубликована: Май 28, 2021

The COVID-19 pandemic has disrupted life throughout the world. Newly developed vaccines promise relief to people who live in high-income countries, although and expensive new treatments are unlikely arrive time help low-and middle-income countries. pathogenesis of is characterized by endothelial dysfunction. Several widely available drugs like statins, ACE inhibitors (ACEIs) angiotensin receptor blockers (ARBs) have immunometabolic activities that (among other things) maintain or restore cell function. For this reason, we undertook an observational study four Belgian hospitals determine whether in-hospital treatment with these could improve survival 959 patients. We found statins ACEIs/ARBs reduced 28-day mortality hospitalized Moreover, combination resulted a 3-fold reduction odds hospital (OR = 0.33; 95% CI 0.17–0.69). These findings were general agreement published studies. Additional studies clinical trials needed convincingly show ACEIs/ARBs, especially their saves lives.

Язык: Английский

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