Transcriptomics-based drug repositioning pipeline identifies therapeutic candidates for COVID-19

Abstract The novel SARS-CoV-2 virus emerged in December 2019 and has few effective treatments. We applied a computational drug repositioning pipeline to SARS-CoV-2 differential gene expression signatures derived from publicly available data. We utilized three independent published studies to acquire...

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Autores principales:	Brian L. Le, Gaia Andreoletti, Tomiko Oskotsky, Albert Vallejo-Gracia, Romel Rosales, Katharine Yu, Idit Kosti, Kristoffer E. Leon, Daniel G. Bunis, Christine Li, G. Renuka Kumar, Kris M. White, Adolfo García-Sastre, Melanie Ott, Marina Sirota
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/4c2062c1199f494bb0611974876e19c4
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spelling	oai:doaj.org-article:4c2062c1199f494bb0611974876e19c42021-12-02T17:34:49ZTranscriptomics-based drug repositioning pipeline identifies therapeutic candidates for COVID-1910.1038/s41598-021-91625-12045-2322https://doaj.org/article/4c2062c1199f494bb0611974876e19c42021-06-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-91625-1https://doaj.org/toc/2045-2322Abstract The novel SARS-CoV-2 virus emerged in December 2019 and has few effective treatments. We applied a computational drug repositioning pipeline to SARS-CoV-2 differential gene expression signatures derived from publicly available data. We utilized three independent published studies to acquire or generate lists of differentially expressed genes between control and SARS-CoV-2-infected samples. Using a rank-based pattern matching strategy based on the Kolmogorov–Smirnov Statistic, the signatures were queried against drug profiles from Connectivity Map (CMap). We validated 16 of our top predicted hits in live SARS-CoV-2 antiviral assays in either Calu-3 or 293T-ACE2 cells. Validation experiments in human cell lines showed that 11 of the 16 compounds tested to date (including clofazimine, haloperidol and others) had measurable antiviral activity against SARS-CoV-2. These initial results are encouraging as we continue to work towards a further analysis of these predicted drugs as potential therapeutics for the treatment of COVID-19.Brian L. LeGaia AndreolettiTomiko OskotskyAlbert Vallejo-GraciaRomel RosalesKatharine YuIdit KostiKristoffer E. LeonDaniel G. BunisChristine LiG. Renuka KumarKris M. WhiteAdolfo García-SastreMelanie OttMarina SirotaNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-14 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Brian L. Le Gaia Andreoletti Tomiko Oskotsky Albert Vallejo-Gracia Romel Rosales Katharine Yu Idit Kosti Kristoffer E. Leon Daniel G. Bunis Christine Li G. Renuka Kumar Kris M. White Adolfo García-Sastre Melanie Ott Marina Sirota Transcriptomics-based drug repositioning pipeline identifies therapeutic candidates for COVID-19
description	Abstract The novel SARS-CoV-2 virus emerged in December 2019 and has few effective treatments. We applied a computational drug repositioning pipeline to SARS-CoV-2 differential gene expression signatures derived from publicly available data. We utilized three independent published studies to acquire or generate lists of differentially expressed genes between control and SARS-CoV-2-infected samples. Using a rank-based pattern matching strategy based on the Kolmogorov–Smirnov Statistic, the signatures were queried against drug profiles from Connectivity Map (CMap). We validated 16 of our top predicted hits in live SARS-CoV-2 antiviral assays in either Calu-3 or 293T-ACE2 cells. Validation experiments in human cell lines showed that 11 of the 16 compounds tested to date (including clofazimine, haloperidol and others) had measurable antiviral activity against SARS-CoV-2. These initial results are encouraging as we continue to work towards a further analysis of these predicted drugs as potential therapeutics for the treatment of COVID-19.
format	article
author	Brian L. Le Gaia Andreoletti Tomiko Oskotsky Albert Vallejo-Gracia Romel Rosales Katharine Yu Idit Kosti Kristoffer E. Leon Daniel G. Bunis Christine Li G. Renuka Kumar Kris M. White Adolfo García-Sastre Melanie Ott Marina Sirota
author_facet	Brian L. Le Gaia Andreoletti Tomiko Oskotsky Albert Vallejo-Gracia Romel Rosales Katharine Yu Idit Kosti Kristoffer E. Leon Daniel G. Bunis Christine Li G. Renuka Kumar Kris M. White Adolfo García-Sastre Melanie Ott Marina Sirota
author_sort	Brian L. Le
title	Transcriptomics-based drug repositioning pipeline identifies therapeutic candidates for COVID-19
title_short	Transcriptomics-based drug repositioning pipeline identifies therapeutic candidates for COVID-19
title_full	Transcriptomics-based drug repositioning pipeline identifies therapeutic candidates for COVID-19
title_fullStr	Transcriptomics-based drug repositioning pipeline identifies therapeutic candidates for COVID-19
title_full_unstemmed	Transcriptomics-based drug repositioning pipeline identifies therapeutic candidates for COVID-19
title_sort	transcriptomics-based drug repositioning pipeline identifies therapeutic candidates for covid-19
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/4c2062c1199f494bb0611974876e19c4
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Transcriptomics-based drug repositioning pipeline identifies therapeutic candidates for COVID-19

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