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Multi-Tissue Transcriptomic-Informed In Silico Investigation of Drugs for the Treatment of Dengue Fever Disease

Transcriptomics, proteomics and pathogen-host interactomics data are being explored for the in silico–informed selection of drugs, prior to their functional evaluation. The effectiveness of this kind of strategy has been put to the test in the current COVID-19 pandemic, and it has been paying off, l...

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Autores principales: Sierra, Beatriz, Magalhães, Ana Cristina, Soares, Daniel, Cavadas, Bruno, Perez, Ana B., Alvarez, Mayling, Aguirre, Eglis, Bracho, Claudia, Pereira, Luisa, Guzman, Maria G.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8402662/
https://www.ncbi.nlm.nih.gov/pubmed/34452405
http://dx.doi.org/10.3390/v13081540
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author Sierra, Beatriz
Magalhães, Ana Cristina
Soares, Daniel
Cavadas, Bruno
Perez, Ana B.
Alvarez, Mayling
Aguirre, Eglis
Bracho, Claudia
Pereira, Luisa
Guzman, Maria G.
author_facet Sierra, Beatriz
Magalhães, Ana Cristina
Soares, Daniel
Cavadas, Bruno
Perez, Ana B.
Alvarez, Mayling
Aguirre, Eglis
Bracho, Claudia
Pereira, Luisa
Guzman, Maria G.
author_sort Sierra, Beatriz
collection PubMed
description Transcriptomics, proteomics and pathogen-host interactomics data are being explored for the in silico–informed selection of drugs, prior to their functional evaluation. The effectiveness of this kind of strategy has been put to the test in the current COVID-19 pandemic, and it has been paying off, leading to a few drugs being rapidly repurposed as treatment against SARS-CoV-2 infection. Several neglected tropical diseases, for which treatment remains unavailable, would benefit from informed in silico investigations of drugs, as performed in this work for Dengue fever disease. We analyzed transcriptomic data in the key tissues of liver, spleen and blood profiles and verified that despite transcriptomic differences due to tissue specialization, the common mechanisms of action, “Adrenergic receptor antagonist”, “ATPase inhibitor”, “NF-kB pathway inhibitor” and “Serotonin receptor antagonist”, were identified as druggable (e.g., oxprenolol, digoxin, auranofin and palonosetron, respectively) to oppose the effects of severe Dengue infection in these tissues. These are good candidates for future functional evaluation and clinical trials.
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spelling pubmed-84026622021-08-29 Multi-Tissue Transcriptomic-Informed In Silico Investigation of Drugs for the Treatment of Dengue Fever Disease Sierra, Beatriz Magalhães, Ana Cristina Soares, Daniel Cavadas, Bruno Perez, Ana B. Alvarez, Mayling Aguirre, Eglis Bracho, Claudia Pereira, Luisa Guzman, Maria G. Viruses Article Transcriptomics, proteomics and pathogen-host interactomics data are being explored for the in silico–informed selection of drugs, prior to their functional evaluation. The effectiveness of this kind of strategy has been put to the test in the current COVID-19 pandemic, and it has been paying off, leading to a few drugs being rapidly repurposed as treatment against SARS-CoV-2 infection. Several neglected tropical diseases, for which treatment remains unavailable, would benefit from informed in silico investigations of drugs, as performed in this work for Dengue fever disease. We analyzed transcriptomic data in the key tissues of liver, spleen and blood profiles and verified that despite transcriptomic differences due to tissue specialization, the common mechanisms of action, “Adrenergic receptor antagonist”, “ATPase inhibitor”, “NF-kB pathway inhibitor” and “Serotonin receptor antagonist”, were identified as druggable (e.g., oxprenolol, digoxin, auranofin and palonosetron, respectively) to oppose the effects of severe Dengue infection in these tissues. These are good candidates for future functional evaluation and clinical trials. MDPI 2021-08-04 /pmc/articles/PMC8402662/ /pubmed/34452405 http://dx.doi.org/10.3390/v13081540 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Sierra, Beatriz
Magalhães, Ana Cristina
Soares, Daniel
Cavadas, Bruno
Perez, Ana B.
Alvarez, Mayling
Aguirre, Eglis
Bracho, Claudia
Pereira, Luisa
Guzman, Maria G.
Multi-Tissue Transcriptomic-Informed In Silico Investigation of Drugs for the Treatment of Dengue Fever Disease
title Multi-Tissue Transcriptomic-Informed In Silico Investigation of Drugs for the Treatment of Dengue Fever Disease
title_full Multi-Tissue Transcriptomic-Informed In Silico Investigation of Drugs for the Treatment of Dengue Fever Disease
title_fullStr Multi-Tissue Transcriptomic-Informed In Silico Investigation of Drugs for the Treatment of Dengue Fever Disease
title_full_unstemmed Multi-Tissue Transcriptomic-Informed In Silico Investigation of Drugs for the Treatment of Dengue Fever Disease
title_short Multi-Tissue Transcriptomic-Informed In Silico Investigation of Drugs for the Treatment of Dengue Fever Disease
title_sort multi-tissue transcriptomic-informed in silico investigation of drugs for the treatment of dengue fever disease
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8402662/
https://www.ncbi.nlm.nih.gov/pubmed/34452405
http://dx.doi.org/10.3390/v13081540
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