Identification of candidate repurposable drugs to combat COVID-19 using a signature-based approach

Abstract The COVID-19 pandemic caused by the novel SARS-CoV-2 is more contagious than other coronaviruses and has higher rates of mortality than influenza. Identification of effective therapeutics is a crucial tool to treat those infected with SARS-CoV-2 and limit the spread of this novel disease gl...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Sinead M. O’Donovan, Ali Imami, Hunter Eby, Nicholas D. Henkel, Justin Fortune Creeden, Sophie Asah, Xiaolu Zhang, Xiaojun Wu, Rawan Alnafisah, R. Travis Taylor, James Reigle, Alexander Thorman, Behrouz Shamsaei, Jarek Meller, Robert E. McCullumsmith
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/183b0c4e766e453cac438874bd544e5b
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:183b0c4e766e453cac438874bd544e5b
record_format	dspace
spelling	oai:doaj.org-article:183b0c4e766e453cac438874bd544e5b2021-12-02T13:34:51ZIdentification of candidate repurposable drugs to combat COVID-19 using a signature-based approach10.1038/s41598-021-84044-92045-2322https://doaj.org/article/183b0c4e766e453cac438874bd544e5b2021-02-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-84044-9https://doaj.org/toc/2045-2322Abstract The COVID-19 pandemic caused by the novel SARS-CoV-2 is more contagious than other coronaviruses and has higher rates of mortality than influenza. Identification of effective therapeutics is a crucial tool to treat those infected with SARS-CoV-2 and limit the spread of this novel disease globally. We deployed a bioinformatics workflow to identify candidate drugs for the treatment of COVID-19. Using an “omics” repository, the Library of Integrated Network-Based Cellular Signatures (LINCS), we simultaneously probed transcriptomic signatures of putative COVID-19 drugs and publicly available SARS-CoV-2 infected cell lines to identify novel therapeutics. We identified a shortlist of 20 candidate drugs: 8 are already under trial for the treatment of COVID-19, the remaining 12 have antiviral properties and 6 have antiviral efficacy against coronaviruses specifically, in vitro. All candidate drugs are either FDA approved or are under investigation. Our candidate drug findings are discordant with (i.e., reverse) SARS-CoV-2 transcriptome signatures generated in vitro, and a subset are also identified in transcriptome signatures generated from COVID-19 patient samples, like the MEK inhibitor selumetinib. Overall, our findings provide additional support for drugs that are already being explored as therapeutic agents for the treatment of COVID-19 and identify promising novel targets that are worthy of further investigation.Sinead M. O’DonovanAli ImamiHunter EbyNicholas D. HenkelJustin Fortune CreedenSophie AsahXiaolu ZhangXiaojun WuRawan AlnafisahR. Travis TaylorJames ReigleAlexander ThormanBehrouz ShamsaeiJarek MellerRobert E. McCullumsmithNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-12 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Sinead M. O’Donovan Ali Imami Hunter Eby Nicholas D. Henkel Justin Fortune Creeden Sophie Asah Xiaolu Zhang Xiaojun Wu Rawan Alnafisah R. Travis Taylor James Reigle Alexander Thorman Behrouz Shamsaei Jarek Meller Robert E. McCullumsmith Identification of candidate repurposable drugs to combat COVID-19 using a signature-based approach
description	Abstract The COVID-19 pandemic caused by the novel SARS-CoV-2 is more contagious than other coronaviruses and has higher rates of mortality than influenza. Identification of effective therapeutics is a crucial tool to treat those infected with SARS-CoV-2 and limit the spread of this novel disease globally. We deployed a bioinformatics workflow to identify candidate drugs for the treatment of COVID-19. Using an “omics” repository, the Library of Integrated Network-Based Cellular Signatures (LINCS), we simultaneously probed transcriptomic signatures of putative COVID-19 drugs and publicly available SARS-CoV-2 infected cell lines to identify novel therapeutics. We identified a shortlist of 20 candidate drugs: 8 are already under trial for the treatment of COVID-19, the remaining 12 have antiviral properties and 6 have antiviral efficacy against coronaviruses specifically, in vitro. All candidate drugs are either FDA approved or are under investigation. Our candidate drug findings are discordant with (i.e., reverse) SARS-CoV-2 transcriptome signatures generated in vitro, and a subset are also identified in transcriptome signatures generated from COVID-19 patient samples, like the MEK inhibitor selumetinib. Overall, our findings provide additional support for drugs that are already being explored as therapeutic agents for the treatment of COVID-19 and identify promising novel targets that are worthy of further investigation.
format	article
author	Sinead M. O’Donovan Ali Imami Hunter Eby Nicholas D. Henkel Justin Fortune Creeden Sophie Asah Xiaolu Zhang Xiaojun Wu Rawan Alnafisah R. Travis Taylor James Reigle Alexander Thorman Behrouz Shamsaei Jarek Meller Robert E. McCullumsmith
author_facet	Sinead M. O’Donovan Ali Imami Hunter Eby Nicholas D. Henkel Justin Fortune Creeden Sophie Asah Xiaolu Zhang Xiaojun Wu Rawan Alnafisah R. Travis Taylor James Reigle Alexander Thorman Behrouz Shamsaei Jarek Meller Robert E. McCullumsmith
author_sort	Sinead M. O’Donovan
title	Identification of candidate repurposable drugs to combat COVID-19 using a signature-based approach
title_short	Identification of candidate repurposable drugs to combat COVID-19 using a signature-based approach
title_full	Identification of candidate repurposable drugs to combat COVID-19 using a signature-based approach
title_fullStr	Identification of candidate repurposable drugs to combat COVID-19 using a signature-based approach
title_full_unstemmed	Identification of candidate repurposable drugs to combat COVID-19 using a signature-based approach
title_sort	identification of candidate repurposable drugs to combat covid-19 using a signature-based approach
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/183b0c4e766e453cac438874bd544e5b
work_keys_str_mv	AT sineadmodonovan identificationofcandidaterepurposabledrugstocombatcovid19usingasignaturebasedapproach AT aliimami identificationofcandidaterepurposabledrugstocombatcovid19usingasignaturebasedapproach AT huntereby identificationofcandidaterepurposabledrugstocombatcovid19usingasignaturebasedapproach AT nicholasdhenkel identificationofcandidaterepurposabledrugstocombatcovid19usingasignaturebasedapproach AT justinfortunecreeden identificationofcandidaterepurposabledrugstocombatcovid19usingasignaturebasedapproach AT sophieasah identificationofcandidaterepurposabledrugstocombatcovid19usingasignaturebasedapproach AT xiaoluzhang identificationofcandidaterepurposabledrugstocombatcovid19usingasignaturebasedapproach AT xiaojunwu identificationofcandidaterepurposabledrugstocombatcovid19usingasignaturebasedapproach AT rawanalnafisah identificationofcandidaterepurposabledrugstocombatcovid19usingasignaturebasedapproach AT rtravistaylor identificationofcandidaterepurposabledrugstocombatcovid19usingasignaturebasedapproach AT jamesreigle identificationofcandidaterepurposabledrugstocombatcovid19usingasignaturebasedapproach AT alexanderthorman identificationofcandidaterepurposabledrugstocombatcovid19usingasignaturebasedapproach AT behrouzshamsaei identificationofcandidaterepurposabledrugstocombatcovid19usingasignaturebasedapproach AT jarekmeller identificationofcandidaterepurposabledrugstocombatcovid19usingasignaturebasedapproach AT robertemccullumsmith identificationofcandidaterepurposabledrugstocombatcovid19usingasignaturebasedapproach
_version_	1718392719379791872

Identification of candidate repurposable drugs to combat COVID-19 using a signature-based approach

Ejemplares similares