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 primary drug targets and the SARS-CoV-2-host interactome in the human protein-protein interaction network. COVID-CDR prioritizes drug combinations with 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 a 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.
•COVID-CDR is an integrative platform for in silico repositioning of drug combinations•It prioritizes drugs with potential to interfere with viral or host-virus functions•It prioritizes potentially synergistic combinations with complementary modes of action•It also provides much useful drug information, all in one intuitive online platform
Repurposing of existing medications has been the mainstream focus of anti-COVID-19 drug discovery as it offers rapid and cost-effective solutions for therapeutic development. Repurposing a combination of therapeutic options with complementary but varying mechanisms of action remains a challenge. Our ability to identify effective combinations is limited due to the vast number of possible drug pairs and a lack of convenient tools that can systematically guide the prioritization of a large range of individual drugs or drug combinations with potential value for the treatment of COVID-19. To address this resource gap, we developed COVID-CDR, an integrative network pharmacology-based platform for in silico repositioning of drug combinations. COVID-CDR provides a visual representation of the cellular interactome involved in modes of action of the chosen drugs and can be used to quantitatively prioritize drug combinations with the potential to act synergistically against COVID-19.
We present COVID-CDR, a web-based computational platform for in silico repositioning of drug combinations against SARS-CoV-2 infection. COVID-CDR constructs a multi-level interactome encompassing drug-target, target-human, and viral-human interactions overlaid on a human PPI network. By leveraging this interactome, COVID-CDR prioritizes potentially synergistic drug combinations as those whose primary targets are in close vicinity to SARS-CoV-2 proteins but holds distinct PPI footprints. The platform also provides diverse information on drugs/drug pairs, offering a multi-evidence solution for investigating drug combination strategies against COVID-19.