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

Over 313,000 SARS-CoV-2 positive cases have been confirmed in Italy as of 30 September 2020, and the number of deaths exceeding thirty-five thousand makes Italy among the list of most significantly affected countries in the world. Such an enormous occurrence of infections and death raises the urgent...

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Autores principales: Teodori, Laura, Sestili, Piero, Madiai, Valeria, Coppari, Sofia, Fraternale, Daniele, Rocchi, Marco Bruno Luigi, Ramakrishna, Seeram, Albertini, Maria Cristina
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7753186/
https://www.ncbi.nlm.nih.gov/pubmed/33363465
http://dx.doi.org/10.3389/fphar.2020.582003
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author Teodori, Laura
Sestili, Piero
Madiai, Valeria
Coppari, Sofia
Fraternale, Daniele
Rocchi, Marco Bruno Luigi
Ramakrishna, Seeram
Albertini, Maria Cristina
author_facet Teodori, Laura
Sestili, Piero
Madiai, Valeria
Coppari, Sofia
Fraternale, Daniele
Rocchi, Marco Bruno Luigi
Ramakrishna, Seeram
Albertini, Maria Cristina
author_sort Teodori, Laura
collection PubMed
description Over 313,000 SARS-CoV-2 positive cases have been confirmed in Italy as of 30 September 2020, and the number of deaths exceeding thirty-five thousand makes Italy among the list of most significantly affected countries in the world. Such an enormous occurrence of infections and death raises the urgent demand for effective available treatments. Discovering the cellular/molecular mechanisms of SARS-CoV-2 pathogenicity is of paramount importance to understand how the infection becomes a disease and how to plan any therapeutic approach. In this regard, we performed an in silico analysis to predict the putative virus targets and evidence the already available therapeutics. Literature experimental results identified angiotensin-converting enzyme ACE and Spike proteins particularly involved in COVID-19. Consequently, we investigated the signalling pathways modulated by the two proteins through query miRNet, the platform linking miRNAs, targets, and functions. Our bioinformatics analysis predicted microRNAs (miRs), miR-335-5p and miR-26b-5p, as being modulated by Spike and ACE together with histone deacetylate (HDAC) pathway. Notably, our results identified ACE/ACE2-ATR1-Cholesterol-HDAC axis signals that also matched with some available clinical data. We hypothesize that the current and EMA-approved, SARS-CoV-2 off-label HDAC inhibitors (HDACis) drugs may be repurposed to limit or block host-virus interactions. Moreover, a ranked list of compounds is provided for further evaluation for safety, efficacy, and effectiveness.
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spelling pubmed-77531862020-12-23 MicroRNAs Bioinformatics Analyses Identifying HDAC Pathway as a Putative Target for Existing Anti‐COVID‐19 Therapeutics Teodori, Laura Sestili, Piero Madiai, Valeria Coppari, Sofia Fraternale, Daniele Rocchi, Marco Bruno Luigi Ramakrishna, Seeram Albertini, Maria Cristina Front Pharmacol Pharmacology Over 313,000 SARS-CoV-2 positive cases have been confirmed in Italy as of 30 September 2020, and the number of deaths exceeding thirty-five thousand makes Italy among the list of most significantly affected countries in the world. Such an enormous occurrence of infections and death raises the urgent demand for effective available treatments. Discovering the cellular/molecular mechanisms of SARS-CoV-2 pathogenicity is of paramount importance to understand how the infection becomes a disease and how to plan any therapeutic approach. In this regard, we performed an in silico analysis to predict the putative virus targets and evidence the already available therapeutics. Literature experimental results identified angiotensin-converting enzyme ACE and Spike proteins particularly involved in COVID-19. Consequently, we investigated the signalling pathways modulated by the two proteins through query miRNet, the platform linking miRNAs, targets, and functions. Our bioinformatics analysis predicted microRNAs (miRs), miR-335-5p and miR-26b-5p, as being modulated by Spike and ACE together with histone deacetylate (HDAC) pathway. Notably, our results identified ACE/ACE2-ATR1-Cholesterol-HDAC axis signals that also matched with some available clinical data. We hypothesize that the current and EMA-approved, SARS-CoV-2 off-label HDAC inhibitors (HDACis) drugs may be repurposed to limit or block host-virus interactions. Moreover, a ranked list of compounds is provided for further evaluation for safety, efficacy, and effectiveness. Frontiers Media S.A. 2020-12-08 /pmc/articles/PMC7753186/ /pubmed/33363465 http://dx.doi.org/10.3389/fphar.2020.582003 Text en Copyright © 2020 Teodori, Sestili, Madiai, Coppari, Fraternale, Rocchi, Ramakrishna and Albertini http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Pharmacology
Teodori, Laura
Sestili, Piero
Madiai, Valeria
Coppari, Sofia
Fraternale, Daniele
Rocchi, Marco Bruno Luigi
Ramakrishna, Seeram
Albertini, Maria Cristina
MicroRNAs Bioinformatics Analyses Identifying HDAC Pathway as a Putative Target for Existing Anti‐COVID‐19 Therapeutics
title MicroRNAs Bioinformatics Analyses Identifying HDAC Pathway as a Putative Target for Existing Anti‐COVID‐19 Therapeutics
title_full MicroRNAs Bioinformatics Analyses Identifying HDAC Pathway as a Putative Target for Existing Anti‐COVID‐19 Therapeutics
title_fullStr MicroRNAs Bioinformatics Analyses Identifying HDAC Pathway as a Putative Target for Existing Anti‐COVID‐19 Therapeutics
title_full_unstemmed MicroRNAs Bioinformatics Analyses Identifying HDAC Pathway as a Putative Target for Existing Anti‐COVID‐19 Therapeutics
title_short MicroRNAs Bioinformatics Analyses Identifying HDAC Pathway as a Putative Target for Existing Anti‐COVID‐19 Therapeutics
title_sort micrornas bioinformatics analyses identifying hdac pathway as a putative target for existing anti‐covid‐19 therapeutics
topic Pharmacology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7753186/
https://www.ncbi.nlm.nih.gov/pubmed/33363465
http://dx.doi.org/10.3389/fphar.2020.582003
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