Transcriptomics-based drug repositioning pipeline identifies therapeutic candidates for COVID-19.
Journal
Scientific reports
ISSN: 2045-2322
Titre abrégé: Sci Rep
Pays: England
ID NLM: 101563288
Informations de publication
Date de publication:
10 06 2021
10 06 2021
Historique:
received:
15
03
2021
accepted:
17
05
2021
entrez:
11
6
2021
pubmed:
12
6
2021
medline:
29
6
2021
Statut:
epublish
Résumé
The novel SARS-CoV-2 virus emerged in December 2019 and has few effective treatments. We applied a computational drug repositioning pipeline to SARS-CoV-2 differential gene expression signatures derived from publicly available data. We utilized three independent published studies to acquire or generate lists of differentially expressed genes between control and SARS-CoV-2-infected samples. Using a rank-based pattern matching strategy based on the Kolmogorov-Smirnov Statistic, the signatures were queried against drug profiles from Connectivity Map (CMap). We validated 16 of our top predicted hits in live SARS-CoV-2 antiviral assays in either Calu-3 or 293T-ACE2 cells. Validation experiments in human cell lines showed that 11 of the 16 compounds tested to date (including clofazimine, haloperidol and others) had measurable antiviral activity against SARS-CoV-2. These initial results are encouraging as we continue to work towards a further analysis of these predicted drugs as potential therapeutics for the treatment of COVID-19.
Identifiants
pubmed: 34112877
doi: 10.1038/s41598-021-91625-1
pii: 10.1038/s41598-021-91625-1
pmc: PMC8192542
doi:
Substances chimiques
Antiviral Agents
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.
Langues
eng
Sous-ensembles de citation
IM
Pagination
12310Subventions
Organisme : NIAID NIH HHS
ID : T32 AI007334
Pays : United States
Organisme : NIGMS NIH HHS
ID : T32 GM007618
Pays : United States
Organisme : NIH HHS
ID : 5DP1DA038043
Pays : United States
Organisme : NIDA NIH HHS
ID : DP1 DA038043
Pays : United States
Organisme : NIAID NIH HHS
ID : U19 AI135972
Pays : United States
Commentaires et corrections
Type : UpdateOf
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