In a new article published today in Nature Reviews Drug Discovery, the REMEDi4ALL consortium presents an expert overview to help navigate computational approaches in designing and optimising drug repurposing development campaigns.
This comprehensive review consists of:
- A survey of widely used and well-known computational tools involved in drug discovery and drug repurposing, classification of resources and generation of sub-categories.
- An expert evaluation of the resources surveyed by experts from within the REMEDi4ALL consortium and beyond, and collation of these resources in an Open Access online catalogue.
- Application of these resources from the online in-silico drug repurposing catalogue to three real-world drug repurposing case studies from the REMEDi4ALL project.
Why is this needed?
Drug repurposing, the investigation of drugs that have previously been investigated and/or approved in another indication, has been utilised in biomedicine for decades and has come into the fore in the wake of the SARS-CoV-2 pandemic where drugs such as dexamethasone and remdesivir were effectively repurposed for the treatment of COVID-19 Drug repurposing has the potential to provide treatments to patients faster and at a lower cost. Moreover, drug repurposing is relatively common, with an estimated 30% of all FDA-approved drugs given at least one additional indication after approval.
To truly unlock the potential of drug repurposing for patients, researchers need to better understand the different characteristics of a potential repurposed drug and how it can be used for a new condition or indication. Before a repurposed drug can be approved, detailed information is needed on many elements including dosing, formulation and tolerance alongside knowledge of disease biology and how the drug works (its mechanism of action). Many resources have been created to assess potential candidates for repurposing. However, these resources remain fragmented, and it can be challenging to assess which resources are best for specific indications, limiting their potential for individuals working on drug repurposing projects.
To address these challenges, the REMEDi4ALL consortium recognised the need for a joint effort in the evaluation and cataloguing of these computational (in-silico) drug repurposing resources to maximise their impact across the drug repurposing community.
What was done?
The REMEDi4ALL consortium, an EU-funded research initiative to drive forward the repurposing of medicines in Europe, first surveyed and catalogued in-silico resources on drug repurposing including a range of web tools, open access databases and prediction methods (AI-based tools).
Based on the survey results and categorising, experts from the REMEDi4ALL consortium and beyond evaluated these resources to provide a shortlist of the most effective and useful in-silico drug repurposing resources for the community. Finally, the consortium demonstrated the applicability of these tools in real-world REMEDi4ALL drug repurposing case studies on SARS-CoV-2, pancreatic cancer and a rare disease (multiple sulfatase deficiency).
What was found?
The survey was designed to categorise approaches to drug repurposing into two distinct categories with associated benefits and limitations: phenotype-based approaches, which focus on the effects of drugs or combinations in disease models and patient populations, and target-based approaches, which focus on using pre-existing data to identify drugs which could interact with targets associated with a specific disease. This allows researchers to more easily find the resources they are looking for depending on the type of drug repurposing application they are working on. The survey also revealed 3 additional categories of drug repurposing approaches based on open-access AI and data mining tools.
Once surveyed, the resources were further divided into a number of subcategories to build the in-silico drug repurposing catalogue. 27 experts evaluated the established and trusted resources in each category through scoring and ranking and identified 15 top-rated resources which are all open-source, mostly accessible and applicable to a range of drug repurposing indications. This work is presented as the in-silico drug repurposing catalogue.
Finally, the REMEDi4ALL partners applied the catalogue to three REMEDi4ALL case studies demonstrating that they were appropriate and useful for distinct repurposing applications and various diseases including rare disease, infections and cancer.
Why does it matter?
The creation of this catalogue by experts in the REMEDi4ALL consortium and beyond is a critical contribution to the drug repurposing space. This catalogue not only details important and relevant resources for individuals working on drug repurposing, but it also provides and entry point for individuals looking to establish the potential of their repurposing candidate using free-to-access online tools and databases. The catalogue provides a guide to researchers involved in drug repurposing and discovery, regardless of their level of computational expertise, and an essential portal for the community which has already been put in practice.
The creation of this web-catalogue was a true community effort, using the expertise of the REMEDi4ALL consortium and other experts in the field to create a sustainable and extendable resource for the drug repurposing community, by the drug repurposing community.
“We believe this in-silico repurposing resource web-catalogue will become of tremendous relevance to many drug development scientists — in all phases of R&D — who themselves are not and do not have the time to become cutting edge computational scientists”.
Tero Aittokallio, corresponding author and Senior Researcher, Institute for Molecular Medicine Finland
How can I find out more?
If you are interested in finding out more about this work you can read the full paper in Nature Reviews Drug Discovery and explore the in-silico drug repurposing catalogue on the REMEDi4ALL website.
If you are interested in finding out more about the REMEDi4ALL project and how to get involved, explore the about us section on our website and connect with us directly or via our multistakeholder LinkedIn forum: Medicines Reimagined.
Want to hear more about the use of computational tools in the drug repurposing landscape? Join us at the International Drug Repurposing Conference (#iDR25) in Amsterdam 7-8 May and join the discussion through a dedicated track on AI in Drug Repurposing. Full conference details and registration link here.
REMEDi4ALL is a Horizon Europe funded project which aims to drive forward the repurposing of medicines across Europe through the creation of a patient-centred, expert-led multistakeholder drug repurposing platform.
