| Literature DB >> 34040048 |
Bruce Schultz1, Andrea Zaliani2,3, Christian Ebeling1, Jeanette Reinshagen2,3, Denisa Bojkova4, Vanessa Lage-Rupprecht1, Reagon Karki1, Sören Lukassen5, Yojana Gadiya1, Neal G Ravindra6, Sayoni Das7, Shounak Baksi8, Daniel Domingo-Fernández1, Manuel Lentzen1, Mark Strivens7, Tamara Raschka1, Jindrich Cinatl4, Lauren Nicole DeLong1, Phil Gribbon2,3, Gerd Geisslinger3,9,10, Sandra Ciesek10,4,11, David van Dijk6, Steve Gardner7, Alpha Tom Kodamullil1, Holger Fröhlich1, Manuel Peitsch12, Marc Jacobs1, Julia Hoeng12, Roland Eils5, Carsten Claussen2,3, Martin Hofmann-Apitius13.
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.Entities:
Year: 2021 PMID： 34040048 DOI： 10.1038/s41598-021-90296-2
Source DB: PubMed Journal: Sci Rep ISSN： 2045-2322 Impact factor: 4.379