Multiscale interactome analysis coupled with off-target drug predictions reveals drug repurposing candidates for human coronavirus disease.
Antiviral Agents
/ pharmacology
Benzamides
/ pharmacology
Cell Line
Computer Simulation
Coronavirus
/ chemistry
Databases, Pharmaceutical
Drug Development
/ methods
Drug Discovery
/ methods
Drug Repositioning
/ methods
Host-Pathogen Interactions
Humans
Imidazoles
/ pharmacology
Interleukin-1 Receptor-Associated Kinases
/ metabolism
SARS-CoV-2
/ chemistry
Triazines
/ pharmacology
COVID-19 Drug Treatment
Journal
Scientific reports
ISSN: 2045-2322
Titre abrégé: Sci Rep
Pays: England
ID NLM: 101563288
Informations de publication
Date de publication:
02 12 2021
02 12 2021
Historique:
received:
15
06
2021
accepted:
03
11
2021
entrez:
3
12
2021
pubmed:
4
12
2021
medline:
15
12
2021
Statut:
epublish
Résumé
The COVID-19 pandemic has highlighted the urgent need for the identification of new antiviral drug therapies for a variety of diseases. COVID-19 is caused by infection with the human coronavirus SARS-CoV-2, while other related human coronaviruses cause diseases ranging from severe respiratory infections to the common cold. We developed a computational approach to identify new antiviral drug targets and repurpose clinically-relevant drug compounds for the treatment of a range of human coronavirus diseases. Our approach is based on graph convolutional networks (GCN) and involves multiscale host-virus interactome analysis coupled to off-target drug predictions. Cell-based experimental assessment reveals several clinically-relevant drug repurposing candidates predicted by the in silico analyses to have antiviral activity against human coronavirus infection. In particular, we identify the MET inhibitor capmatinib as having potent and broad antiviral activity against several coronaviruses in a MET-independent manner, as well as novel roles for host cell proteins such as IRAK1/4 in supporting human coronavirus infection, which can inform further drug discovery studies.
Identifiants
pubmed: 34857794
doi: 10.1038/s41598-021-02432-7
pii: 10.1038/s41598-021-02432-7
pmc: PMC8640055
doi:
Substances chimiques
Antiviral Agents
0
Benzamides
0
Imidazoles
0
Triazines
0
IRAK1 protein, human
EC 2.7.11.1
IRAK4 protein, human
EC 2.7.11.1
Interleukin-1 Receptor-Associated Kinases
EC 2.7.11.1
capmatinib
TY34L4F9OZ
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
23315Informations de copyright
© 2021. The Author(s).
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