A method for the rational selection of drug repurposing candidates from multimodal knowledge harmonization
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.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2021 |
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| Erschienen: |
2021 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:11 |
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| Enthalten in: |
Scientific reports - 11(2021), 1 vom: 26. Mai, Seite 11049 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Schultz, Bruce [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 09.06.2021 Date Revised 01.11.2023 published: Electronic Citation Status MEDLINE |
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| doi: |
10.1038/s41598-021-90296-2 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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NLM325889430 |
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| 245 | 1 | 2 | |a A method for the rational selection of drug repurposing candidates from multimodal knowledge harmonization |
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| 520 | |a 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 | ||
| 650 | 4 | |a Journal Article | |
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| 700 | 1 | |a Ebeling, Christian |e verfasserin |4 aut | |
| 700 | 1 | |a Reinshagen, Jeanette |e verfasserin |4 aut | |
| 700 | 1 | |a Bojkova, Denisa |e verfasserin |4 aut | |
| 700 | 1 | |a Lage-Rupprecht, Vanessa |e verfasserin |4 aut | |
| 700 | 1 | |a Karki, Reagon |e verfasserin |4 aut | |
| 700 | 1 | |a Lukassen, Sören |e verfasserin |4 aut | |
| 700 | 1 | |a Gadiya, Yojana |e verfasserin |4 aut | |
| 700 | 1 | |a Ravindra, Neal G |e verfasserin |4 aut | |
| 700 | 1 | |a Das, Sayoni |e verfasserin |4 aut | |
| 700 | 1 | |a Baksi, Shounak |e verfasserin |4 aut | |
| 700 | 1 | |a Domingo-Fernández, Daniel |e verfasserin |4 aut | |
| 700 | 1 | |a Lentzen, Manuel |e verfasserin |4 aut | |
| 700 | 1 | |a Strivens, Mark |e verfasserin |4 aut | |
| 700 | 1 | |a Raschka, Tamara |e verfasserin |4 aut | |
| 700 | 1 | |a Cinatl, Jindrich |e verfasserin |4 aut | |
| 700 | 1 | |a DeLong, Lauren Nicole |e verfasserin |4 aut | |
| 700 | 1 | |a Gribbon, Phil |e verfasserin |4 aut | |
| 700 | 1 | |a Geisslinger, Gerd |e verfasserin |4 aut | |
| 700 | 1 | |a Ciesek, Sandra |e verfasserin |4 aut | |
| 700 | 1 | |a van Dijk, David |e verfasserin |4 aut | |
| 700 | 1 | |a Gardner, Steve |e verfasserin |4 aut | |
| 700 | 1 | |a Kodamullil, Alpha Tom |e verfasserin |4 aut | |
| 700 | 1 | |a Fröhlich, Holger |e verfasserin |4 aut | |
| 700 | 1 | |a Peitsch, Manuel |e verfasserin |4 aut | |
| 700 | 1 | |a Jacobs, Marc |e verfasserin |4 aut | |
| 700 | 1 | |a Hoeng, Julia |e verfasserin |4 aut | |
| 700 | 1 | |a Eils, Roland |e verfasserin |4 aut | |
| 700 | 1 | |a Claussen, Carsten |e verfasserin |4 aut | |
| 700 | 1 | |a Hofmann-Apitius, Martin |e verfasserin |4 aut | |
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