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

Abstract

<p>Repurposing of the existing medications has become the mainstream focus of anti-COVID-19 drug discovery as it offers rapid and cost-effective solutions for therapeutic development. However, there is still a great deal to enhance efficacy of repurposing therapeutic options through combination therapy, in which promising drugs with varying mechanisms of action are administered together. Nonetheless, our ability to identify and validate effective combinations is limited due to the huge number of possible drug pairs. Yet, there is no available resource which can systematically guide to identify or choose the effective individual drugs or best possible synergistic drug combinations for the treatment of SARS-CoV-2 infection. To address this resource gap, we developed a web-based platform that displays the network-based mechanism of action of drug combinations, thus simultaneously giving a visual of the cellular interactome involved in the mode of action of the chosen drugs. The platform allows the freedom to choose two or more drug combinations and provides the options to investigate network-based efficacy of drug combinations and understand the similarity score, primary indications, and contraindications of using these drugs combinations. In a nutshell, the platform (accessible via: <a href="http://vafaeelab.com/COVID19_repositioning.html">http://vafaeelab.com/COVID19_repositioning.html</a>) is of the first of its type which provides a systematic approach for pre-clinical investigation of combination therapy for treating COVID-19 on the fingertips of the clinicians or researchers.</p>

Ageing impairs the airway epithelium defence response to SARS-CoV-2

“…Drug repositioning has gained considerable interest during the COVID-19 pandemic to accelerate the identification and approval of beneficial therapeutic drugs. We assessed whether the age-specific transcriptional response of hNECs to SARS-CoV-2 infection may influence the efficacy of therapeutic agents by implementing a modified version of the COVID-19 Combinational Drug Repositioning (COVID-CDR) platform 40 . To screen for potential repositionable drugs across different age groups, we calculated the network proximity between drug targets and SARS-CoV-2-interacting host proteins as an unbiased measure of drug-disease relatedness.…”