This is a preprint, a preliminary version of a manuscript that has not completed peer review at a journal. Research Square does not conduct peer review prior to posting preprints. The posting of a preprint on this server should not be interpreted as an endorsement of its validity or suitability for dissemination as established information or for guiding clinical practice.
Biological Sciences - Article
George Spyrou
Cyprus Institute of Neurology and Genetics
Corresponding Author
ORCiD: https://orcid.org/0000-0002-2470-3363
License:
This work is licensed under a CC BY 4.0 License. Read Full License
The SARS-CoV-2 pandemic is undeniably the most severe global health emergency since the 1918 Influenza outbreak. Depending on its evolutionary trajectory, the virus is expected to establish itself as an endemic infectious respiratory disease exhibiting seasonal flare-ups. Therefore, despite the unprecedented rally to reach a vaccine that can offer widespread immunization, it is equally important to reach effective prevention and treatment regimens for COVID-19. Contributing to this effort, we have curated and analyzed multi-source and multi-omics publicly available data from patients, cell lines and databases in order to fuel a multiplex computational drug repurposing approach. We devised a Network-based integration of multi-omic data to prioritize the most important genes related to COVID-19 and subsequently rerank the identified candidate drugs. We concluded to a highly informed integrated drug shortlist by combining structural diversity filtering along with experts’ curation and drug-target mapping on the depicted molecular pathways. In addition to the recently proposed drugs that are already generating promising results such as dexamethasone and remdesivir, our list includes inhibitors of Src Tyrosine Kinase (bosutinib, dasatinib, cytarabine and saracatinib) which appear to be involved in multiple COVID-19 pathophysiological mechanisms. In addition, we highlight specific immunomodulators and anti-inflamatory drugs like dactolisib and methotrexate and inhibitors of histone deacetylase like hydroquinone and vorinostat with potential beneficial effects in their mechanisms of action.
Keywords
Multi-omics data integration, network-based analysis, multiplex drug repurposing approach, COVID-19, integrated drug shortlist
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Figure 5
This preprint is available for download as a PDF.
There is NO Competing Interest.
This is a list of supplementary files associated with this preprint. Click to download.
- SupplementaryFile1.xlsx
Top 150 over- and under-expressed genes/proteins/metabolites – regulators
- supplement1.xlsx
Top 150 over- and under-expressed genes/proteins/metabolites – regulators
- SupplementaryFile2.xlsx
GWAS analysis
- supplement2.xlsx
GWAS analysis
- supplement3.xlsx
Top 50 and Top 20 drug lists
- SupplementaryFile3.xlsx
Top 50 and Top 20 drug lists
- SupplementaryFile4.xlsx
Integration Scores
- supplement4.xlsx
Integration Scores
- SupplementaryFile5.xlsx
Complete antiviral drugs from TaxAV and HPAV
- supplement5.xlsx
Complete antiviral drugs from TaxAV and HPAV
- SupplementaryFile6.pdf
Detailed table of the top 65 drugs
- supplement6.pdf
Detailed table of the top 65 drugs
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This is a preprint, a preliminary version of a manuscript that has not completed peer review at a journal. Research Square does not conduct peer review prior to posting preprints. The posting of a preprint on this server should not be interpreted as an endorsement of its validity or suitability for dissemination as established information or for guiding clinical practice.
Biological Sciences - Article
George Spyrou
Cyprus Institute of Neurology and Genetics
Corresponding Author
ORCiD: https://orcid.org/0000-0002-2470-3363
Badges
Prescreen
This manuscript passed our Prescreen assessment
Complete author information
Appropriate declaration statements
Potential risks to human health
Prescreen
History
CURRENT STATUS: Posted
View the published article at Briefings in Bioinformatics.
Version 1
Posted 18 Sep, 2020
No community comments so far
Metrics
Comments: 0
PDF Downloads: ...
HTML Views: ...
License:
This work is licensed under a CC BY 4.0 License. Read Full License
View the published article at Briefings in Bioinformatics.
The SARS-CoV-2 pandemic is undeniably the most severe global health emergency since the 1918 Influenza outbreak. Depending on its evolutionary trajectory, the virus is expected to establish itself as an endemic infectious respiratory disease exhibiting seasonal flare-ups. Therefore, despite the unprecedented rally to reach a vaccine that can offer widespread immunization, it is equally important to reach effective prevention and treatment regimens for COVID-19. Contributing to this effort, we have curated and analyzed multi-source and multi-omics publicly available data from patients, cell lines and databases in order to fuel a multiplex computational drug repurposing approach. We devised a Network-based integration of multi-omic data to prioritize the most important genes related to COVID-19 and subsequently rerank the identified candidate drugs. We concluded to a highly informed integrated drug shortlist by combining structural diversity filtering along with experts’ curation and drug-target mapping on the depicted molecular pathways. In addition to the recently proposed drugs that are already generating promising results such as dexamethasone and remdesivir, our list includes inhibitors of Src Tyrosine Kinase (bosutinib, dasatinib, cytarabine and saracatinib) which appear to be involved in multiple COVID-19 pathophysiological mechanisms. In addition, we highlight specific immunomodulators and anti-inflamatory drugs like dactolisib and methotrexate and inhibitors of histone deacetylase like hydroquinone and vorinostat with potential beneficial effects in their mechanisms of action.
Figure 1
Figure 1
Figure 2
Figure 2
Figure 3
Figure 3
Figure 4
Figure 4
Figure 5
Figure 5
This preprint is available for download as a PDF.
There is NO Competing Interest.
This is a list of supplementary files associated with this preprint. Click to download.
- SupplementaryFile1.xlsx
Top 150 over- and under-expressed genes/proteins/metabolites – regulators
- supplement1.xlsx
Top 150 over- and under-expressed genes/proteins/metabolites – regulators
- SupplementaryFile2.xlsx
GWAS analysis
- supplement2.xlsx
GWAS analysis
- supplement3.xlsx
Top 50 and Top 20 drug lists
- SupplementaryFile3.xlsx
Top 50 and Top 20 drug lists
- SupplementaryFile4.xlsx
Integration Scores
- supplement4.xlsx
Integration Scores
- SupplementaryFile5.xlsx
Complete antiviral drugs from TaxAV and HPAV
- supplement5.xlsx
Complete antiviral drugs from TaxAV and HPAV
- SupplementaryFile6.pdf
Detailed table of the top 65 drugs
- supplement6.pdf
Detailed table of the top 65 drugs
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