Drug repurposing improves disease targeting 11-fold on average. New insights from network module targeting and its application to COVID-19.
Inés Rivero, Miguel Castresana, Dimitri Guala, Erik L. L. Sonnhammer · 2020
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, on average, drugs target 4 disease modules, yet the similarity between disease modules targeted by the same drug is generally low and the total number of disease modules targeted per drug increases from 134 to 230 when drug targets are extended Moreover, our results highlight that drug repurposing is more dependent on target proteins 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.