Drug repurposing improves disease targeting 11-fold and can be augmented by network module targeting, applied to COVID-19

This analysis presents a systematic evaluation of the extent of therapeutic opportunities that can be obtained from drug repurposing by connecting drug targets with disease genes. When using FDA-approved indications as a reference level we found that drug repurposing can offer an average of an 11-fo...

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Bibliographic Details
Published in:Scientific reports 2021-10, Vol.11 (1), p.20687-11, Article 20687
Main Authors: Rivero-García, Inés, Castresana-Aguirre, Miguel, Guglielmo, Luca, Guala, Dimitri, Sonnhammer, Erik L. L.
Format: Article
Language:English
Subjects:
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631/154
Antiviral Agents - pharmacology
Bayes Theorem
Computational Biology - methods
Coronaviruses
COVID-19
COVID-19 Drug Treatment
Disease
Drug Delivery Systems
Drug Discovery
Drug Repositioning - methods
Gene Regulatory Networks - drug effects
Humanities and Social Sciences
Humans
multidisciplinary
Polypharmacology
Protein Interaction Mapping
Protein Interaction Maps - genetics
SARS-CoV-2
Science
Science (multidisciplinary)
Therapeutic targets
United States
United States Food and Drug Administration
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Summary:This analysis presents a systematic evaluation of the extent of therapeutic opportunities that can be obtained from drug repurposing by connecting drug targets with disease genes. When using FDA-approved indications as a reference level we found that drug repurposing can offer an average of an 11-fold increase in disease coverage, with the maximum number of diseases covered per drug being increased from 134 to 167 after extending the drug targets with their high confidence first neighbors. Additionally, by network analysis to connect drugs to disease modules we found that drugs on average target 4 disease modules, yet the similarity between disease modules targeted by the same drug is generally low and the maximum number of disease modules targeted per drug increases from 158 to 229 when drug targets are neighbor-extended. Moreover, our results highlight that drug repurposing is more dependent on target proteins being shared between diseases than on polypharmacological properties of drugs. We apply our drug repurposing and network module analysis to COVID-19 and show that Fostamatinib is the drug with the highest module coverage.
ISSN:2045-2322
2045-2322
DOI:10.1038/s41598-021-99721-y