An integrative drug repositioning framework discovered a potential therapeutic agent targeting COVID-19.
Signal Transduct Target Ther
; 6(1): 165, 2021 04 24.
Article
in English
| MEDLINE | ID: covidwho-1199266
ABSTRACT
The global spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) requires an urgent need to find effective therapeutics for the treatment of coronavirus disease 2019 (COVID-19). In this study, we developed an integrative drug repositioning framework, which fully takes advantage of machine learning and statistical analysis approaches to systematically integrate and mine large-scale knowledge graph, literature and transcriptome data to discover the potential drug candidates against SARS-CoV-2. Our in silico screening followed by wet-lab validation indicated that a poly-ADP-ribose polymerase 1 (PARP1) inhibitor, CVL218, currently in Phase I clinical trial, may be repurposed to treat COVID-19. Our in vitro assays revealed that CVL218 can exhibit effective inhibitory activity against SARS-CoV-2 replication without obvious cytopathic effect. In addition, we showed that CVL218 can interact with the nucleocapsid (N) protein of SARS-CoV-2 and is able to suppress the LPS-induced production of several inflammatory cytokines that are highly relevant to the prevention of immunopathology induced by SARS-CoV-2 infection.
Full text:
Available
Collection:
International databases
Database:
MEDLINE
Main subject:
Antiviral Agents
/
Computer Simulation
/
Drug Repositioning
/
SARS-CoV-2
/
COVID-19
/
COVID-19 Drug Treatment
/
Models, Biological
Type of study:
Prognostic study
/
Randomized controlled trials
Limits:
Humans
Language:
English
Journal:
Signal Transduct Target Ther
Year:
2021
Document Type:
Article
Affiliation country:
S41392-021-00568-6
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