Integrative resource for network-based investigation of COVID-19 combinatorial drug repositioning and mechanism of action

A K M Azad; Shadma Fatima; Alexander Capraro; Shafagh A Waters; Fatemeh Vafaee

doi:10.1016/j.patter.2021.100325

Integrative resource for network-based investigation of COVID-19 combinatorial drug repositioning and mechanism of action

Patterns (N Y). 2021 Sep 10;2(9):100325. doi: 10.1016/j.patter.2021.100325. Epub 2021 Jul 14.

Authors

A K M Azad¹, Shadma Fatima^{1

2}, Alexander Capraro^{3

4}, Shafagh A Waters^{3

4

5}, Fatemeh Vafaee^{1

6}

Affiliations

¹ School of Biotechnology and Biomolecular Sciences, University of New South Wales (UNSW Sydney), Sydney, NSW 2052, Australia.
² Department of Medical Oncology, Ingham Institute of Applied Research, Sydney, Australia.
³ School of Women's and Children's Health, Faculty of Medicine, UNSW Sydney, Sydney, NSW, Australia.
⁴ Molecular and Integrative Cystic Fibrosis Research Centre, UNSW Sydney and Sydney Children's Hospital, Sydney, Australia.
⁵ Department of Respiratory Medicine, Sydney Children's Hospital, Sydney, NSW, Australia.
⁶ Data Science Hub, University of New South Wales, Kensington, NSW, Australia.

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.

Keywords: COVID-19; PPI; SARS-CoV-2; combination therapy; complementary exposure; drug repositioning; drug targets; mechanisms of action; network pharmacology; protein-protein interaction.