Identification of SARS-CoV-2–induced pathways reveals drug repurposing strategies
| Autor: | Patrick Schmerer, Tony Kouzarides, Eliza Yankova, Anika Liu, Konstantinos Tzelepis, Ulrike Felgenhauer, Rebecca Harris, Winnie Lei, Friedemann Weber, Méabh MacMahon, Alison J. Schuldt, Woochang Hwang, Nicholas M Katritsis, Namshik Han, Frank McCaughan, Kathryn Chapman |
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| Přispěvatelé: | Han, Namshik [0000-0002-7741-6384], Hwang, Woochang [0000-0003-0876-7305], Tzelepis, Konstantinos [0000-0002-4865-7648], Schmerer, Patrick [0000-0003-2617-3199], Yankova, Eliza [0000-0003-2913-0012], MacMahon, Méabh [0000-0003-3477-2941], Lei, Winnie [0000-0002-1108-6394], M Katritsis, Nicholas [0000-0002-0635-1712], Liu, Anika [0000-0002-8561-4700], Felgenhauer, Ulrike [0000-0002-9478-5368], McCaughan, Frank [0000-0002-8012-7524], Weber, Friedemann [0000-0001-9737-337X], Kouzarides, Tony [0000-0002-8918-4162], Apollo - University of Cambridge Repository |
| Jazyk: | angličtina |
| Předmět: |
Proguanil
Computational biology Disease Virus Replication Antiviral Agents 03 medical and health sciences 0302 clinical medicine Immune system Sulfasalazine ComputerApplications_MISCELLANEOUS Medicine Humans Research Articles Repurposing 030304 developmental biology 0303 health sciences Multidisciplinary business.industry SARS-CoV-2 Drug Repositioning SciAdv r-articles Life Sciences COVID-19 3. Good health COVID-19 Drug Treatment Coronavirus Clinical trial Drug repositioning Viral replication Computer Science Neural Networks Computer business 030217 neurology & neurosurgery Research Article medicine.drug |
| Zdroj: | Science Advances |
| ISSN: | 2375-2548 |
| DOI: | 10.1126/sciadv.abh3032 |
| Popis: | Data-driven computational analysis and simulation identified drug repurposing opportunities for COVID-19. The global outbreak of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) necessitates the rapid development of new therapies against coronavirus disease 2019 (COVID-19) infection. Here, we present the identification of 200 approved drugs, appropriate for repurposing against COVID-19. We constructed a SARS-CoV-2–induced protein network, based on disease signatures defined by COVID-19 multiomics datasets, and cross-examined these pathways against approved drugs. This analysis identified 200 drugs predicted to target SARS-CoV-2–induced pathways, 40 of which are already in COVID-19 clinical trials, testifying to the validity of the approach. Using artificial neural network analysis, we classified these 200 drugs into nine distinct pathways, within two overarching mechanisms of action (MoAs): viral replication (126) and immune response (74). Two drugs (proguanil and sulfasalazine) implicated in viral replication were shown to inhibit replication in cell assays. This unbiased and validated analysis opens new avenues for the rapid repurposing of approved drugs into clinical trials. |
| Databáze: | OpenAIRE |
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