학술논문
A method for the rational selection of drug repurposing candidates from multimodal knowledge harmonization.
Document Type
Article
Author
Schultz, Bruce; Zaliani, Andrea; Ebeling, Christian; Reinshagen, Jeanette; Bojkova, Denisa; Lage-Rupprecht, Vanessa; Karki, Reagon; Lukassen, Sören; Gadiya, Yojana; Ravindra, Neal G.; Das, Sayoni; Baksi, Shounak; Domingo-Fernández, Daniel; Lentzen, Manuel; Strivens, Mark; Raschka, Tamara; Cinatl, Jindrich; DeLong, Lauren Nicole; Gribbon, Phil; Geisslinger, Gerd
Source
Subject
*SARS-CoV-2
*COVID-19 pandemic
*TARGETED drug delivery
*NELFINAVIR
*RALOXIFENE
*REMDESIVIR
*DRUG repositioning
*
*
*
*
*
*
Language
ISSN
2045-2322
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. [ABSTRACT FROM AUTHOR]