A method for the rational selection of drug repurposing candidates from multimodal knowledge harmonization

Abstract The SARS-CoV-2 pandemic has challenged researchers at a global scale. The scientific community’s massive response has resulted in a flood of experiments, analyses, hypotheses, and publications, especially in the field of drug repurposing. However, many of the proposed therapeutic compounds...

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Autores principales:	Bruce Schultz, Andrea Zaliani, Christian Ebeling, Jeanette Reinshagen, Denisa Bojkova, Vanessa Lage-Rupprecht, Reagon Karki, Sören Lukassen, Yojana Gadiya, Neal G. Ravindra, Sayoni Das, Shounak Baksi, Daniel Domingo-Fernández, Manuel Lentzen, Mark Strivens, Tamara Raschka, Jindrich Cinatl, Lauren Nicole DeLong, Phil Gribbon, Gerd Geisslinger, Sandra Ciesek, David van Dijk, Steve Gardner, Alpha Tom Kodamullil, Holger Fröhlich, Manuel Peitsch, Marc Jacobs, Julia Hoeng, Roland Eils, Carsten Claussen, Martin Hofmann-Apitius
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/18b0a7d14b824058a3306b2a9990465c
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spelling	oai:doaj.org-article:18b0a7d14b824058a3306b2a9990465c2021-12-02T15:00:50ZA method for the rational selection of drug repurposing candidates from multimodal knowledge harmonization10.1038/s41598-021-90296-22045-2322https://doaj.org/article/18b0a7d14b824058a3306b2a9990465c2021-05-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-90296-2https://doaj.org/toc/2045-2322Abstract The SARS-CoV-2 pandemic has challenged researchers at a global scale. The scientific community’s massive response has resulted in a flood of experiments, analyses, hypotheses, and publications, especially in the field of drug repurposing. However, many of the proposed therapeutic compounds obtained from SARS-CoV-2 specific assays are not in agreement and thus demonstrate the need for a singular source of COVID-19 related information from which a rational selection of drug repurposing candidates can be made. In this paper, we present the COVID-19 PHARMACOME, a comprehensive drug-target-mechanism graph generated from a compilation of 10 separate disease maps and sources of experimental data focused on SARS-CoV-2/COVID-19 pathophysiology. By applying our systematic approach, we were able to predict the synergistic effect of specific drug pairs, such as Remdesivir and Thioguanosine or Nelfinavir and Raloxifene, on SARS-CoV-2 infection. Experimental validation of our results demonstrate that our graph can be used to not only explore the involved mechanistic pathways, but also to identify novel combinations of drug repurposing candidates.Bruce SchultzAndrea ZalianiChristian EbelingJeanette ReinshagenDenisa BojkovaVanessa Lage-RupprechtReagon KarkiSören LukassenYojana GadiyaNeal G. RavindraSayoni DasShounak BaksiDaniel Domingo-FernándezManuel LentzenMark StrivensTamara RaschkaJindrich CinatlLauren Nicole DeLongPhil GribbonGerd GeisslingerSandra CiesekDavid van DijkSteve GardnerAlpha Tom KodamullilHolger FröhlichManuel PeitschMarc JacobsJulia HoengRoland EilsCarsten ClaussenMartin Hofmann-ApitiusNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-10 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Bruce Schultz Andrea Zaliani Christian Ebeling Jeanette Reinshagen Denisa Bojkova Vanessa Lage-Rupprecht Reagon Karki Sören Lukassen Yojana Gadiya Neal G. Ravindra Sayoni Das Shounak Baksi Daniel Domingo-Fernández Manuel Lentzen Mark Strivens Tamara Raschka Jindrich Cinatl Lauren Nicole DeLong Phil Gribbon Gerd Geisslinger Sandra Ciesek David van Dijk Steve Gardner Alpha Tom Kodamullil Holger Fröhlich Manuel Peitsch Marc Jacobs Julia Hoeng Roland Eils Carsten Claussen Martin Hofmann-Apitius A method for the rational selection of drug repurposing candidates from multimodal knowledge harmonization
description	Abstract The SARS-CoV-2 pandemic has challenged researchers at a global scale. The scientific community’s massive response has resulted in a flood of experiments, analyses, hypotheses, and publications, especially in the field of drug repurposing. However, many of the proposed therapeutic compounds obtained from SARS-CoV-2 specific assays are not in agreement and thus demonstrate the need for a singular source of COVID-19 related information from which a rational selection of drug repurposing candidates can be made. In this paper, we present the COVID-19 PHARMACOME, a comprehensive drug-target-mechanism graph generated from a compilation of 10 separate disease maps and sources of experimental data focused on SARS-CoV-2/COVID-19 pathophysiology. By applying our systematic approach, we were able to predict the synergistic effect of specific drug pairs, such as Remdesivir and Thioguanosine or Nelfinavir and Raloxifene, on SARS-CoV-2 infection. Experimental validation of our results demonstrate that our graph can be used to not only explore the involved mechanistic pathways, but also to identify novel combinations of drug repurposing candidates.
format	article
author	Bruce Schultz Andrea Zaliani Christian Ebeling Jeanette Reinshagen Denisa Bojkova Vanessa Lage-Rupprecht Reagon Karki Sören Lukassen Yojana Gadiya Neal G. Ravindra Sayoni Das Shounak Baksi Daniel Domingo-Fernández Manuel Lentzen Mark Strivens Tamara Raschka Jindrich Cinatl Lauren Nicole DeLong Phil Gribbon Gerd Geisslinger Sandra Ciesek David van Dijk Steve Gardner Alpha Tom Kodamullil Holger Fröhlich Manuel Peitsch Marc Jacobs Julia Hoeng Roland Eils Carsten Claussen Martin Hofmann-Apitius
author_facet	Bruce Schultz Andrea Zaliani Christian Ebeling Jeanette Reinshagen Denisa Bojkova Vanessa Lage-Rupprecht Reagon Karki Sören Lukassen Yojana Gadiya Neal G. Ravindra Sayoni Das Shounak Baksi Daniel Domingo-Fernández Manuel Lentzen Mark Strivens Tamara Raschka Jindrich Cinatl Lauren Nicole DeLong Phil Gribbon Gerd Geisslinger Sandra Ciesek David van Dijk Steve Gardner Alpha Tom Kodamullil Holger Fröhlich Manuel Peitsch Marc Jacobs Julia Hoeng Roland Eils Carsten Claussen Martin Hofmann-Apitius
author_sort	Bruce Schultz
title	A method for the rational selection of drug repurposing candidates from multimodal knowledge harmonization
title_short	A method for the rational selection of drug repurposing candidates from multimodal knowledge harmonization
title_full	A method for the rational selection of drug repurposing candidates from multimodal knowledge harmonization
title_fullStr	A method for the rational selection of drug repurposing candidates from multimodal knowledge harmonization
title_full_unstemmed	A method for the rational selection of drug repurposing candidates from multimodal knowledge harmonization
title_sort	method for the rational selection of drug repurposing candidates from multimodal knowledge harmonization
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/18b0a7d14b824058a3306b2a9990465c
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A method for the rational selection of drug repurposing candidates from multimodal knowledge harmonization

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