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

Published version
Peer-reviewed

Type

Article

Change log

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.

Description

Keywords

Antiviral Agents, COVID-19, Drug Repositioning, Humans, Neural Networks, Computer, Proguanil, SARS-CoV-2, Sulfasalazine, Virus Replication, COVID-19 Drug Treatment

Journal Title

Sci Adv

Conference Name

Journal ISSN

2375-2548
2375-2548

Volume Title

7

Publisher

American Association for the Advancement of Science (AAAS)
Sponsorship
Wellcome Trust (210926/Z/18/Z)