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Identification of SARS-CoV-2-induced pathways reveals drug repurposing strategies.
Han, Namshik; Hwang, Woochang; Tzelepis, Konstantinos; Schmerer, Patrick; Yankova, Eliza; MacMahon, Méabh; Lei, Winnie; M Katritsis, Nicholas; Liu, Anika; Felgenhauer, Ulrike; Schuldt, Alison; Harris, Rebecca; Chapman, Kathryn; McCaughan, Frank; Weber, Friedemann; Kouzarides, Tony.
  • Han N; Milner Therapeutics Institute, University of Cambridge, Cambridge, UK. n.han@milner.cam.ac.uk t.kouzarides@gurdon.cam.ac.uk.
  • Hwang W; Milner Therapeutics Institute, University of Cambridge, Cambridge, UK.
  • Tzelepis K; Milner Therapeutics Institute, University of Cambridge, Cambridge, UK.
  • Schmerer P; Institute for Virology, FB10-Veterinary Medicine, Justus-Liebig University, Gießen 35392, Germany.
  • Yankova E; Milner Therapeutics Institute, University of Cambridge, Cambridge, UK.
  • MacMahon M; Milner Therapeutics Institute, University of Cambridge, Cambridge, UK.
  • Lei W; Centre for Therapeutics Discovery, LifeArc, Stevenage, UK.
  • M Katritsis N; Milner Therapeutics Institute, University of Cambridge, Cambridge, UK.
  • Liu A; Department of Surgery, University of Cambridge, Cambridge, UK.
  • Felgenhauer U; Milner Therapeutics Institute, University of Cambridge, Cambridge, UK.
  • Schuldt A; Department of Chemical Engineering and Biotechnology, University of Cambridge, Cambridge, UK.
  • Harris R; Milner Therapeutics Institute, University of Cambridge, Cambridge, UK.
  • Chapman K; Department of Chemistry, University of Cambridge, Cambridge, UK.
  • McCaughan F; Data and Computational Sciences, GSK, London, UK.
  • Weber F; Institute for Virology, FB10-Veterinary Medicine, Justus-Liebig University, Gießen 35392, Germany.
  • Kouzarides T; Milner Therapeutics Institute, University of Cambridge, Cambridge, UK.
Sci Adv ; 7(27)2021 06.
Article in English | MEDLINE | ID: covidwho-1290607
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ABSTRACT
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.
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Full text: Available Collection: International databases Database: MEDLINE Main subject: Drug Repositioning / SARS-CoV-2 Type of study: Prognostic study / Randomized controlled trials Limits: Humans Language: English Year: 2021 Document Type: Article

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Full text: Available Collection: International databases Database: MEDLINE Main subject: Drug Repositioning / SARS-CoV-2 Type of study: Prognostic study / Randomized controlled trials Limits: Humans Language: English Year: 2021 Document Type: Article