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dc.contributor.authorHwang, Woochang
dc.contributor.authorHan, Namshik
dc.date.accessioned2022-01-28T00:31:27Z
dc.date.available2022-01-28T00:31:27Z
dc.date.issued2021-11-09
dc.identifier.issn1046-2023
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/332983
dc.description.abstractIn the past 20 years, there have been several infectious disease outbreaks in humans for which the causative agent has been a zoonotic coronavirus. Novel infectious disease outbreaks, as illustrated by the current coronavirus disease 2019 (COVID-19) pandemic, demand a rapid response in terms of identifying effective treatments for seriously ill patients. The repurposing of approved drugs from other therapeutic areas is one of the most practical routes through which to approach this. Here, we present a systematic network-based drug repurposing methodology, which interrogates virus-human, human protein-protein and drug-protein interactome data. We identified 196 approved drugs that are appropriate for repurposing against COVID-19 and 102 approved drugs against a related coronavirus, severe acute respiratory syndrome (SARS-CoV). We constructed a protein-protein interaction (PPI) network based on disease signatures from COVID-19 and SARS multi-omics datasets. Analysis of this PPI network uncovered key pathways. Of the 196 drugs predicted to target COVID-19 related pathways, 44 (hypergeometric p-value: 1.98e-04) are already in COVID-19 clinical trials, demonstrating the validity of our approach. Using an artificial neural network, we provide information on the mechanism of action and therapeutic value for each of the identified drugs, to facilitate their rapid repurposing into clinical trials.
dc.format.mediumPrint-Electronic
dc.publisherElsevier BV
dc.rightsAttribution-NonCommercial-NoDerivatives 4.0 International
dc.rights.urihttps://creativecommons.org/licenses/by-nc-nd/4.0/
dc.subjectArtificial neural network
dc.subjectCOVID-19
dc.subjectCoronavirus
dc.subjectDrug mechanism
dc.subjectDrug repurposing
dc.subjectSARS
dc.subjectVirus replication
dc.titleIdentification of potential pan-coronavirus therapies using a computational drug repurposing platform.
dc.typeArticle
dc.publisher.departmentMilner Therapeutics Institute
dc.date.updated2022-01-27T13:59:26Z
prism.publicationDate2021
prism.publicationNameMethods
dc.identifier.doi10.17863/CAM.80407
dcterms.dateAccepted2021-11-03
rioxxterms.versionofrecord10.1016/j.ymeth.2021.11.002
rioxxterms.versionVoR
dc.contributor.orcidHan, Namshik [0000-0002-7741-6384]
dc.identifier.eissn1095-9130
rioxxterms.typeJournal Article/Review
cam.depositDate2022-01-27
pubs.licence-identifierapollo-deposit-licence-2-1
pubs.licence-display-nameApollo Repository Deposit Licence Agreement


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Attribution-NonCommercial-NoDerivatives 4.0 International
Except where otherwise noted, this item's licence is described as Attribution-NonCommercial-NoDerivatives 4.0 International