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

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.

Anti-SARS-CoV-2 Strategies and the Potential Role of miRNA in the Assessment of COVID-19 Morbidity, Recurrence, and Therapy

“…Knowing those facts would increase the chances of identifying potential prognostic markers and targets that would provide more efficient pandemic extinguishing. So far, we are focused on two approaches, i.e., looking for analogy in other pandemics and using the drugs/strategies that already exist or identifying novel ones [42]. However, apart from a pretty obvious solution, i.e., vaccination (will be addressed further), there are still some alternative approaches that we consider.…”

Peering Into Avian Influenza A(H5N8) for a Framework towards Pandemic Preparedness

“…With proteomics data of IAVs [95,96], proteomic analyses can be performed to identify novel drug targets and drug repurposing strategies as previously applied to SARS-CoV-2 [97]. Taking a host-directed therapy approach [98], the constructed SARS-CoV-2induced protein artificial neural network cross-examined disease signatures and approved drugs, identifying 200 drugs with 40 already in clinical trials and 2 (proguanil and sulfasalazine) demonstrated to inhibit replication [97]. Applying such an approach to the H5N8 subtype and extended IAVs, understanding these metabolic perturbations are key in identifying novel and repurposing existing drugs to target them [99].…”

Identification of potential pan-coronavirus therapies using a computational drug repurposing platform

“…Previously, we have applied a drug repurposing strategy to identify potential new treatments for COVID-19 [7] . In this study, we use a similar computational approach, but include datasets from cells infected with either SARS-CoV-2 or SARS-CoV.…”