Network medicine framework for identifying drug-repurposing opportunities for COVID-19

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dc.contributor.authorGysi, Deisy Morselli
dc.contributor.authorDo Valle, Ítalo
dc.contributor.authorZitnik, Marinka
dc.contributor.authorAmeli, Asher
dc.contributor.authorGan, Xiao
dc.contributor.authorVarol, Onur
dc.contributor.authorGhiassian, Susan Dina
dc.contributor.authorPatten, J. J.
dc.contributor.authorDavey, Robert A.
dc.contributor.authorLoscalzo, Joseph
dc.contributor.authorBarabási, Albert László
dc.contributor.institutionDepartment of Network and Data Science
dc.date.accessioned2025-04-08T09:10:02Z
dc.date.available2025-04-08T09:10:02Z
dc.date.issued2021-05-11
dc.description.abstractThe COVID-19 pandemic has highlighted the need to quickly and reliably prioritize clinically approved compounds for their potential effectiveness for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections. Here, we deployed algorithms relying on artificial intelligence, network diffusion, and network proximity, tasking each of them to rank 6,340 drugs for their expected efficacy against SARS-CoV-2. To test the predictions, we used as ground truth 918 drugs experimentally screened in VeroE6 cells, as well as the list of drugs in clinical trials that capture the medical community's assessment of drugs with potential COVID-19 efficacy. We find that no single predictive algorithm offers consistently reliable outcomes across all datasets and metrics. This outcome prompted us to develop a multimodal technology that fuses the predictions of all algorithms, finding that a consensus among the different predictive methods consistently exceeds the performance of the best individual pipelines. We screened in human cells the top-ranked drugs, obtaining a 62% success rate, in contrast to the 0.8% hit rate of nonguided screenings. Of the six drugs that reduced viral infection, four could be directly repurposed to treat COVID-19, proposing novel treatments for COVID-19. We also found that 76 of the 77 drugs that successfully reduced viral infection do not bind the proteins targeted by SARS-CoV-2, indicating that these network drugs rely on network-based mechanisms that cannot be identified using docking-based strategies. These advances offer a methodological pathway to identify repurposable drugs for future pathogens and neglected diseases underserved by the costs and extended timeline of de novo drug development.eng
dc.identifier.citationGysi, D M, Do Valle, Í, Zitnik, M, Ameli, A, Gan, X, Varol, O, Ghiassian, S D, Patten, J J, Davey, R A, Loscalzo, J & Barabási, A L 2021, 'Network medicine framework for identifying drug-repurposing opportunities for COVID-19', Proceedings of the National Academy of Sciences of the United States of America, vol. 118, no. 19, e2025581118. https://doi.org/10.1073/pnas.2025581118
dc.identifier.doi10.1073/pnas.2025581118
dc.identifier.issn0027-8424
dc.identifier.issn1091-6490
dc.identifier.urihttps://hdl.handle.net/20.500.14018/27144
dc.identifier.urlhttp://www.scopus.com/inward/record.url?scp=85105060638&partnerID=8YFLogxK
dc.language.isoeng
dc.rightscc-by
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/
dc.source.journaltitleProceedings of the National Academy of Sciences of the United States of America
dc.subjectDrug repurposing
dc.subjectInfectious diseases
dc.subjectNetwork medicine
dc.subjectSystems biology
dc.subjectMultidisciplinary
dc.subjectSDG 3 - Good Health and Well-being
dc.titleNetwork medicine framework for identifying drug-repurposing opportunities for COVID-19eng
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