Scientific Reports (May 2021)
A method for the rational selection of drug repurposing candidates from multimodal knowledge harmonization
- 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
Affiliations
- Bruce Schultz
- Fraunhofer Institute for Algorithms and Scientific Computing SCAI, Department of Bioinformatics, Institutszentrum Birlinghoven
- Andrea Zaliani
- ScreeningPort, Fraunhofer Institute for Translational Medicine and Pharmacology ITMP
- Christian Ebeling
- Fraunhofer Institute for Algorithms and Scientific Computing SCAI, Department of Bioinformatics, Institutszentrum Birlinghoven
- Jeanette Reinshagen
- ScreeningPort, Fraunhofer Institute for Translational Medicine and Pharmacology ITMP
- Denisa Bojkova
- Institute for Medical Virology, University Hospital Frankfurt
- Vanessa Lage-Rupprecht
- Fraunhofer Institute for Algorithms and Scientific Computing SCAI, Department of Bioinformatics, Institutszentrum Birlinghoven
- Reagon Karki
- Fraunhofer Institute for Algorithms and Scientific Computing SCAI, Department of Bioinformatics, Institutszentrum Birlinghoven
- Sören Lukassen
- Center for Digital Health, Berlin Institute of Health (BIH), Charité Universitätsmedizin Berlin
- Yojana Gadiya
- Fraunhofer Institute for Algorithms and Scientific Computing SCAI, Department of Bioinformatics, Institutszentrum Birlinghoven
- Neal G. Ravindra
- Center for Biomedical Data Science, Yale School of Medicine, Yale University
- Sayoni Das
- Unit 8B Bankside, PrecisionLife Ltd.
- Shounak Baksi
- Causality BioModels Pvt Ltd.
- Daniel Domingo-Fernández
- Fraunhofer Institute for Algorithms and Scientific Computing SCAI, Department of Bioinformatics, Institutszentrum Birlinghoven
- Manuel Lentzen
- Fraunhofer Institute for Algorithms and Scientific Computing SCAI, Department of Bioinformatics, Institutszentrum Birlinghoven
- Mark Strivens
- Unit 8B Bankside, PrecisionLife Ltd.
- Tamara Raschka
- Fraunhofer Institute for Algorithms and Scientific Computing SCAI, Department of Bioinformatics, Institutszentrum Birlinghoven
- Jindrich Cinatl
- Institute for Medical Virology, University Hospital Frankfurt
- Lauren Nicole DeLong
- Fraunhofer Institute for Algorithms and Scientific Computing SCAI, Department of Bioinformatics, Institutszentrum Birlinghoven
- Phil Gribbon
- ScreeningPort, Fraunhofer Institute for Translational Medicine and Pharmacology ITMP
- Gerd Geisslinger
- Fraunhofer Cluster of Excellence for Immune Mediated Diseases, CIMD
- Sandra Ciesek
- Fraunhofer Institute for Translational Medicine and Pharmacology ITMP
- David van Dijk
- Center for Biomedical Data Science, Yale School of Medicine, Yale University
- Steve Gardner
- Unit 8B Bankside, PrecisionLife Ltd.
- Alpha Tom Kodamullil
- Fraunhofer Institute for Algorithms and Scientific Computing SCAI, Department of Bioinformatics, Institutszentrum Birlinghoven
- Holger Fröhlich
- Fraunhofer Institute for Algorithms and Scientific Computing SCAI, Department of Bioinformatics, Institutszentrum Birlinghoven
- Manuel Peitsch
- Philipp Morris International R&D, Biological Systems Research, R&D Innovation Cube T1517.07
- Marc Jacobs
- Fraunhofer Institute for Algorithms and Scientific Computing SCAI, Department of Bioinformatics, Institutszentrum Birlinghoven
- Julia Hoeng
- Philipp Morris International R&D, Biological Systems Research, R&D Innovation Cube T1517.07
- Roland Eils
- Center for Digital Health, Berlin Institute of Health (BIH), Charité Universitätsmedizin Berlin
- Carsten Claussen
- ScreeningPort, Fraunhofer Institute for Translational Medicine and Pharmacology ITMP
- Martin Hofmann-Apitius
- Fraunhofer Institute for Algorithms and Scientific Computing SCAI, Department of Bioinformatics, Institutszentrum Birlinghoven
- DOI
- https://doi.org/10.1038/s41598-021-90296-2
- Journal volume & issue
-
Vol. 11,
no. 1
pp. 1 – 10
Abstract
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.
