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dc.creatorZhou, Yadi
dc.creatorHou, Yuan
dc.creatorShen, Jiayu
dc.creatorHuang, Yin
dc.creatorMartin, William
dc.creatorCheng, Feixiong
dc.date.accessioned2020-07-17T15:23:34Z
dc.date.available2020-07-17T15:23:34Z
dc.date.created2020
dc.identifier.otherhttps://doi.org/10.1038/s41421-020-0153-3spa
dc.identifier.urihttp://hdl.handle.net/20.500.12010/10741
dc.description.abstractHuman coronaviruses (HCoVs), including severe acute respiratory syndrome coronavirus (SARS-CoV) and 2019 novel coronavirus (2019-nCoV, also known as SARS-CoV-2), lead global epidemics with high morbidity and mortality. However, there are currently no effective drugs targeting 2019-nCoV/SARS-CoV-2. Drug repurposing, representing as an effective drug discovery strategy from existing drugs, could shorten the time and reduce the cost compared to de novo drug discovery. In this study, we present an integrative, antiviral drug repurposing methodology implementing a systems pharmacology-based network medicine platform, quantifying the interplay between the HCoV–host interactome and drug targets in the human protein–protein interaction network. Phylogenetic analyses of 15 HCoV whole genomes reveal that 2019-nCoV/SARS-CoV-2 shares the highest nucleotide sequence identity with SARS-CoV (79.7%). Specifically, the envelope and nucleocapsid proteins of 2019-nCoV/SARS-CoV-2 are two evolutionarily conserved regions, having the sequence identities of 96% and 89.6%, respectively, compared to SARS-CoV. Using network proximity analyses of drug targets and HCoV–host interactions in the human interactome, we prioritize 16 potential anti-HCoV repurposable drugs (e.g., melatonin, mercaptopurine, and sirolimus) that are further validated by enrichment analyses of drug-gene signatures and HCoV-induced transcriptomics data in human cell lines. We further identify three potential drug combinations (e.g., sirolimus plus dactinomycin, mercaptopurine plus melatonin, and toremifene plus emodin) captured by the “Complementary Exposure” pattern: the targets of the drugs both hit the HCoV–host subnetwork, but target separate neighborhoods in the human interactome network. In summary, this study offers powerful network-based methodologies for rapid identification of candidate repurposable drugs and potential drug combinations targeting 2019-nCoV/SARS-CoV-2spa
dc.format.extent18 páginasspa
dc.format.mimetypeapplication/pdfspa
dc.publisherScience Directeng
dc.sourcereponame:Expeditio Repositorio Institucional UJTLspa
dc.sourceinstname:Universidad de Bogotá Jorge Tadeo Lozanospa
dc.subjectCoV/SARS-CoV-2spa
dc.subjectCoronavirus 2019spa
dc.subjectNetwork-basedspa
dc.titleNetwork-based drug repurposing for novel coronavirus 2019-nCoV/SARS-CoV-2spa
dc.type.localArtículospa
dc.subject.lembSíndrome respiratorio agudo gravespa
dc.subject.lembCOVID-19spa
dc.subject.lembSARS-CoV-2spa
dc.subject.lembCoronavirusspa
dc.rights.accessrightsinfo:eu-repo/semantics/openAccessspa
dc.type.hasversioninfo:eu-repo/semantics/acceptedVersionspa
dc.identifier.doihttps://doi.org/10.1038/s41421-020-0153-3spa


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