Identification of SARS-CoV-2–induced pathways reveals drug repurposing strategies | Zendy

Namshik Han | Zendy; Woochang Hwang | Zendy; Konstantinos Tzelepis | Zendy; Patrick Schmerer | Zendy; Eliza Yankova | Zendy; Méabh MacMahon | Zendy; Winnie Lei | Zendy; Nicholas M. Katritsis | Zendy; Anika Liu | Zendy; Ulrike Felgenhauer | Zendy; Alison Schuldt | Zendy; Rebecca Harris | Zendy; Kathryn Chapman | Zendy; Frank McCaughan | Zendy; Friedemann Weber | Zendy; Tony Kouzarides | Zendy

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Identification of SARS-CoV-2–induced pathways reveals drug repurposing strategies

Author(s) -

Namshik Han,

Woochang Hwang,

Konstantinos Tzelepis,

Patrick Schmerer,

Eliza Yankova,

Méabh MacMahon,

Winnie Lei,

Nicholas M. Katritsis,

Anika Liu,

Ulrike Felgenhauer,

Alison Schuldt,

Rebecca Harris,

Kathryn Chapman,

Frank McCaughan,

Friedemann Weber,

Tony Kouzarides

Publication year - 2021

Publication title -

science advances

Language(s) - Uncategorized

Resource type - Journals

SCImago Journal Rank - 5.928

H-Index - 146

ISSN - 2375-2548

DOI - 10.1126/sciadv.abh3032

Subject(s) - drug repositioning , repurposing , covid-19 , identification (biology) , drug , drug discovery , computational biology , drug development , virology , biology , computer science , medicine , bioinformatics , pharmacology , infectious disease (medical specialty) , disease , ecology , botany , pathology , outbreak

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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