A comprehensive integrated drug similarity resource for in-silico drug repositioning and beyond

Abstract

Drug similarity studies are driven by the hypothesis that similar drugs should display similar therapeutic actions and thus can potentially treat a similar constellation of diseases. Drug–drug similarity has been derived by variety of direct and indirect sources of evidence and frequently shown high predictive power in discovering validated repositioning candidates as well as other in-silico drug development applications. Yet, existing resources either have limited coverage or rely on an individual source of evidence, overlooking the wealth and diversity of drug-related data sources. Hence, there has been an unmet need for a comprehensive resource integrating diverse drug-related information to derive multi-evidenced drug–drug similarities. We addressed this resource gap by compiling heterogenous information for an exhaustive set of small-molecule drugs (total of 10 367 in the current version) and systematically integrated multiple sources of evidence to derive a multi-modal drug–drug similarity network. The resulting database, ‘DrugSimDB’ currently includes 238 635 drug pairs with significant aggregated similarity, complemented with an interactive user-friendly web interface (http://vafaeelab.com/drugSimDB.html), which not only enables database ease of access, search, filtration and export, but also provides a variety of complementary information on queried drugs and interactions. The integration approach can flexibly incorporate further drug information into the similarity network, providing an easily extendable platform. The database compilation and construction source-code has been well-documented and semi-automated for any-time upgrade to account for new drugs and up-to-date drug information.

An Integrative Resource for Network-Based Investigation of COVID-19 Combinatorial Drug Repositioning and Mechanism of Action

“…Some studies have shown that cyclosporine may dramatically limit the severity of sepsis and/or inflammation-induced acute lung injury and post-cardiac arrest AR in SARS-COV-2 patients [43]. It has been consistently reported to improve lung function via mitochondrial processes, including PTP inhibition [50,51]. Altogether our, network analyses and scientific data suggested that combining LY2275796 and cyclosporin can offer a potential therapeutic approach for SARS-CoV-2.…”

“…Previously, repositioning of existing drugs based on drug-drug similarity, side-effect prediction, drug-drug interaction prediction [7][8][9][10][11] and drug target prediction has received an escalated interest as an innovative drug development strategy offering a quick solution for treatment for various diseases along with the additional benefits of reducing cost, saving time and avoiding risk as few phases of de-novo drug discovery can be bypassed for repositioning candidates [12].…”

Predicting Drug-Disease Association Based on Ensemble Strategy

“…Similarity-based methods are widely used to find similar drugs (Vilar and Hripcsak, 2017 ). Some studies have shown that the use of similarity measures in drug repositioning often shows high predictive power (Azad et al, 2020 ). Therefore, similarity measurement is always regarded as an important step in drug repositioning research.…”

An Integrative Resource for Network-Based Investigation of COVID-19 Combinatorial Drug Repositioning and Mechanism of Action

“…including PTP inhibition [50,51]. Altogether our, network analyses and scientific data suggested that combining LY2275796 and cyclosporin can offer a potential therapeutic approach for SARS-CoV-2.…”