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The COVID-19 PHARMACOME: 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 C. Peitsch
Marc Jacobs
Julia Hoeng
Roland Eils
Carsten Claussen
Martin Hofmann-Apitius
出版
Universitätsbibliothek Johann Christian Senckenberg
, 2021
URL
http://books.google.com.hk/books?id=J5f8zwEACAAJ&hl=&source=gbs_api
註釋
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.