The COVID-19 PHARMACOME: 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 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: |
|
|---|
Preprint| Erscheinungsjahr: |
2022 |
|---|---|
| Erschienen: |
2022 |
| Enthalten in: |
bioRxiv.org - (2022) vom: 20. Nov. Zur Gesamtaufnahme - year:2022 |
|---|
| Sprache: |
Englisch |
|---|
| Beteiligte Personen: |
Schultz, Bruce [VerfasserIn] |
|---|
| Links: |
Volltext [kostenfrei] |
|---|
| Themen: |
|---|
| doi: |
10.1101/2020.09.23.308239 |
|---|
| funding: |
|
|---|---|
| Förderinstitution / Projekttitel: |
|
| PPN (Katalog-ID): |
XBI018808018 |
|---|
| LEADER | 01000caa a22002652 4500 | ||
|---|---|---|---|
| 001 | XBI018808018 | ||
| 003 | DE-627 | ||
| 005 | 20230429100317.0 | ||
| 007 | cr uuu---uuuuu | ||
| 008 | 200924s2022 xx |||||o 00| ||eng c | ||
| 024 | 7 | |a 10.1101/2020.09.23.308239 |2 doi | |
| 035 | |a (DE-627)XBI018808018 | ||
| 035 | |a (biorXiv)10.1101/2020.09.23.308239 | ||
| 040 | |a DE-627 |b ger |c DE-627 |e rakwb | ||
| 041 | |a eng | ||
| 100 | 1 | |a Schultz, Bruce |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a The COVID-19 PHARMACOME: A method for the rational selection of drug repurposing candidates from multimodal knowledge harmonization |
| 264 | 1 | |c 2022 | |
| 336 | |a Text |b txt |2 rdacontent | ||
| 337 | |a Computermedien |b c |2 rdamedia | ||
| 338 | |a Online-Ressource |b cr |2 rdacarrier | ||
| 520 | |a 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. | ||
| 650 | 4 | |a Biology |7 (dpeaa)DE-84 | |
| 650 | 4 | |a 570 |7 (dpeaa)DE-84 | |
| 700 | 1 | |a Zaliani, Andrea |e verfasserin |4 aut | |
| 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 | |
| 773 | 0 | 8 | |i Enthalten in |t bioRxiv.org |g (2022) vom: 20. Nov. |
| 773 | 1 | 8 | |g year:2022 |g day:20 |g month:11 |
| 856 | 4 | 0 | |u http://dx.doi.org/10.1101/2020.09.23.308239 |z kostenfrei |3 Volltext |
| 912 | |a GBV_XBI | ||
| 912 | |a SSG-OLC-PHA | ||
| 951 | |a AR | ||
| 952 | |j 2022 |b 20 |c 11 | ||