Exploring the SARS-CoV-2 virus-host-drug interactome for drug repurposing

Sepideh Sadegh,Mhaned Oubounyt,Julian Späth,Andreas Pichlmair,Josch K Pauling,Tim Daniel Rose,David B Blumenthal,Marisol Salgado-Albarrán,Julian Matschinske,Reza Nasirigerdeh,Markus List,Tim Kacprowski,Alexey Stukalov,Jan Baumbach,Gihanna Galindez,Nina K Wenke,Kevin Yuan

doi:10.1038/s41467-020-17189-2

Abstract

Coronavirus Disease-2019 (COVID-19) is an infectious disease caused by the SARS-CoV-2 virus. Various studies exist about the molecular mechanisms of viral infection. However, such information is spread across many publications and it is very time-consuming to integrate, and exploit. We develop CoVex, an interactive online platform for SARS-CoV-2 host interactome exploration and drug (target) identification. CoVex integrates virus-human protein interactions, human protein-protein interactions, and drug-target interactions. It allows visual exploration of the virus-host interactome and implements systems medicine algorithms for network-based prediction of drug candidates. Thus, CoVex is a resource to understand molecular mechanisms of pathogenicity and to prioritize candidate therapeutics. We investigate recent hypotheses on a systems biology level to explore mechanistic virus life cycle drivers, and to extract drug repurposing candidates. CoVex renders COVID-19 drug research systems-medicine-ready by giving the scientific community direct access to network medicine algorithms. It is available at https://exbio.wzw.tum.de/covex/.

Highlights

Coronavirus Disease-2019 (COVID-19) is an infectious disease caused by the SARS-CoV-2 virus
We identify six relevant drugs that target bradykinin receptor B1 (BDKRB1): Ramipril, Captopril, Perindopril, and Enalaprilat, which belong to the angiotensin-converting enzyme (ACE) inhibitor class[15]; Icatibant, an antagonist of the bradykinin receptor B216; and bradykinin, a non-approved drug that is degraded by the ACE17
Using KeyPathwayMiner for drug target discovery followed by closeness centrality for drug discovery, we identify methylene blue in addition to Chloroquine and Deferoxamine, which are both in COVID-19 clinical trials[28,29]

Summary

Introduction

Coronavirus Disease-2019 (COVID-19) is an infectious disease caused by the SARS-CoV-2 virus. We develop CoVex, an interactive online platform for SARS-CoV-2 host interactome exploration and drug (target) identification. CoVex integrates virus-human protein interactions, human protein-protein interactions, and drug-target interactions It allows visual exploration of the virus-host interactome and implements systems medicine algorithms for network-based prediction of drug candidates. CoVex renders COVID-19 drug research systems-medicine-ready by giving the scientific community direct access to network medicine algorithms. Computational systems and network medicine approaches offer a methodological toolbox required to understand molecular virus–host–drug mechanisms and to predict novel drug targets to attack them[8,9]. Few studies on these mechanisms in SARS-CoV-2 exist.

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