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

Abstract

An effective monotherapy to target the complex and multifactorial pathology of SARS-CoV-2 infection poses a challenge to drug repositioning, which can be improved by combination therapy. We developed an online network pharmacology-based drug repositioning platform, COVID-CDR (http://vafaeelab.com/COVID19repositioning.html), that enables a visual and quantitative investigation of the interplay between the drug primary targets and the SARS-CoV-2–host interactome in the human protein-protein interaction network. COVID-CDR prioritizes drug combinations with the potential to act synergistically through different, yet potentially complementary pathways. It provides the options for understanding multi-evidence drug-pair similarity scores along with several other relevant information on individual drugs or drug pairs. Overall, COVID-CDR is the first-of-its-kind online platform that provides a systematic approach for pre-clinical in silico investigation of combination therapies for treating COVID-19 at the fingertips of the clinicians and researchers.