Transcriptome-based drug repositioning for coronavirus disease 2019 (COVID-19).
Antiviral Agents
/ pharmacology
Betacoronavirus
/ drug effects
Bronchoalveolar Lavage Fluid
/ chemistry
COVID-19
Cell Degranulation
/ immunology
Coronavirus Infections
/ drug therapy
Drug Repositioning
Endocytosis
/ immunology
Gene Expression Profiling
Humans
Lysosomes
/ immunology
Molecular Docking Simulation
Neutrophil Activation
/ immunology
Pandemics
Pneumonia, Viral
/ drug therapy
Ribavirin
/ pharmacology
SARS-CoV-2
Saquinavir
/ pharmacology
Transcriptome
COVID-19
SARS-CoV-2
drug repositioning
neutrophil degranulation
saquinavir, ribavirin
Journal
Pathogens and disease
ISSN: 2049-632X
Titre abrégé: Pathog Dis
Pays: United States
ID NLM: 101595366
Informations de publication
Date de publication:
01 06 2020
01 06 2020
Historique:
received:
20
05
2020
accepted:
07
07
2020
pubmed:
16
7
2020
medline:
4
8
2020
entrez:
16
7
2020
Statut:
ppublish
Résumé
The outbreak of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) around the world has led to a pandemic with high morbidity and mortality. However, there are no effective drugs to prevent and treat the disease. Transcriptome-based drug repositioning, identifying new indications for old drugs, is a powerful tool for drug development. Using bronchoalveolar lavage fluid transcriptome data of COVID-19 patients, we found that the endocytosis and lysosome pathways are highly involved in the disease and that the regulation of genes involved in neutrophil degranulation was disrupted, suggesting an intense battle between SARS-CoV-2 and humans. Furthermore, we implemented a coexpression drug repositioning analysis, cogena, and identified two antiviral drugs (saquinavir and ribavirin) and several other candidate drugs (such as dinoprost, dipivefrine, dexamethasone and (-)-isoprenaline). Notably, the two antiviral drugs have also previously been identified using molecular docking methods, and ribavirin is a recommended drug in the diagnosis and treatment protocol for COVID pneumonia (trial version 5-7) published by the National Health Commission of the P.R. of China. Our study demonstrates the value of the cogena-based drug repositioning method for emerging infectious diseases, improves our understanding of SARS-CoV-2-induced disease, and provides potential drugs for the prevention and treatment of COVID-19 pneumonia.
Identifiants
pubmed: 32667665
pii: 5871823
doi: 10.1093/femspd/ftaa036
pmc: PMC7454646
pii:
doi:
Substances chimiques
Antiviral Agents
0
Ribavirin
49717AWG6K
Saquinavir
L3JE09KZ2F
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Informations de copyright
© FEMS 2020.
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