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Expert-Augmented Computational Drug Repurposing Identified Baricitinib as a Treatment for COVID-19

The onset of the 2019 Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic necessitated the identification of approved drugs to treat the disease, before the development, approval and widespread administration of suitable vaccines. To identify such a drug, we used a visual analytics...

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Autores principales: Smith, Daniel P., Oechsle, Olly, Rawling, Michael J., Savory, Ed, Lacoste, Alix M.B., Richardson, Peter John
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8356560/
https://www.ncbi.nlm.nih.gov/pubmed/34393789
http://dx.doi.org/10.3389/fphar.2021.709856
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author Smith, Daniel P.
Oechsle, Olly
Rawling, Michael J.
Savory, Ed
Lacoste, Alix M.B.
Richardson, Peter John
author_facet Smith, Daniel P.
Oechsle, Olly
Rawling, Michael J.
Savory, Ed
Lacoste, Alix M.B.
Richardson, Peter John
author_sort Smith, Daniel P.
collection PubMed
description The onset of the 2019 Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic necessitated the identification of approved drugs to treat the disease, before the development, approval and widespread administration of suitable vaccines. To identify such a drug, we used a visual analytics workflow where computational tools applied over an AI-enhanced biomedical knowledge graph were combined with human expertise. The workflow comprised rapid augmentation of knowledge graph information from recent literature using machine learning (ML) based extraction, with human-guided iterative queries of the graph. Using this workflow, we identified the rheumatoid arthritis drug baricitinib as both an antiviral and anti-inflammatory therapy. The effectiveness of baricitinib was substantiated by the recent publication of the data from the ACTT-2 randomised Phase 3 trial, followed by emergency approval for use by the FDA, and a report from the CoV-BARRIER trial confirming significant reductions in mortality with baricitinib compared to standard of care. Such methods that iteratively combine computational tools with human expertise hold promise for the identification of treatments for rare and neglected diseases and, beyond drug repurposing, in areas of biological research where relevant data may be lacking or hidden in the mass of available biomedical literature.
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spelling pubmed-83565602021-08-12 Expert-Augmented Computational Drug Repurposing Identified Baricitinib as a Treatment for COVID-19 Smith, Daniel P. Oechsle, Olly Rawling, Michael J. Savory, Ed Lacoste, Alix M.B. Richardson, Peter John Front Pharmacol Pharmacology The onset of the 2019 Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic necessitated the identification of approved drugs to treat the disease, before the development, approval and widespread administration of suitable vaccines. To identify such a drug, we used a visual analytics workflow where computational tools applied over an AI-enhanced biomedical knowledge graph were combined with human expertise. The workflow comprised rapid augmentation of knowledge graph information from recent literature using machine learning (ML) based extraction, with human-guided iterative queries of the graph. Using this workflow, we identified the rheumatoid arthritis drug baricitinib as both an antiviral and anti-inflammatory therapy. The effectiveness of baricitinib was substantiated by the recent publication of the data from the ACTT-2 randomised Phase 3 trial, followed by emergency approval for use by the FDA, and a report from the CoV-BARRIER trial confirming significant reductions in mortality with baricitinib compared to standard of care. Such methods that iteratively combine computational tools with human expertise hold promise for the identification of treatments for rare and neglected diseases and, beyond drug repurposing, in areas of biological research where relevant data may be lacking or hidden in the mass of available biomedical literature. Frontiers Media S.A. 2021-07-28 /pmc/articles/PMC8356560/ /pubmed/34393789 http://dx.doi.org/10.3389/fphar.2021.709856 Text en Copyright © 2021 Smith, Oechsle, Rawling, Savory, Lacoste and Richardson. https://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
Smith, Daniel P.
Oechsle, Olly
Rawling, Michael J.
Savory, Ed
Lacoste, Alix M.B.
Richardson, Peter John
Expert-Augmented Computational Drug Repurposing Identified Baricitinib as a Treatment for COVID-19
title Expert-Augmented Computational Drug Repurposing Identified Baricitinib as a Treatment for COVID-19
title_full Expert-Augmented Computational Drug Repurposing Identified Baricitinib as a Treatment for COVID-19
title_fullStr Expert-Augmented Computational Drug Repurposing Identified Baricitinib as a Treatment for COVID-19
title_full_unstemmed Expert-Augmented Computational Drug Repurposing Identified Baricitinib as a Treatment for COVID-19
title_short Expert-Augmented Computational Drug Repurposing Identified Baricitinib as a Treatment for COVID-19
title_sort expert-augmented computational drug repurposing identified baricitinib as a treatment for covid-19
topic Pharmacology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8356560/
https://www.ncbi.nlm.nih.gov/pubmed/34393789
http://dx.doi.org/10.3389/fphar.2021.709856
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