Discovery of clinically approved drugs capable of inhibiting SARS-CoV-2 in vitro infection using a phenotypic screening strategy and network-analysis to predict their potential to treat covid-19
bioinformatics drug discovery/repurposing therapeutics
Authors:Douglas Ferreira Sales-Medina et al.,
Link to paper: https://www.biorxiv.org/content/10.1101/2020.07.09.196337v2
Tags: Bioinformatics, Drug discovery/Drug repurpose, Therapeutics
Development of an assay to screen clinically approved compounds for antiviral activity against SARS-CoV2.
Discovery of 4 drugs that inhibit SARS-CoV2 infection: brequinar, abiraterone acetate, neomycin, and the extract of Hedera helix.
Functional and network analysis integrate drug activity with known host-virus-interactions.
Sales-Medina et al. developed a microscopy-based screening assay in Vero E6 cells for the discovery of anti-SARS-CoV2 compounds. The authors validated their assay with three drugs already reported to have antiviral activity against SARS-CoV-2 in vitro. By measuring effects on infection and cytotoxicity of 65 clinically approved drugs, the authors identified four drugs which showed selective inhibition of SARS-CoV2 in vitro: brequinar, abiraterone acetate, neomycin and the extract of Hedera helix. Using a data mining-based computational approach, the authors built a drug-molecules-disease/function network to show possible mechanisms of action for the four identified drugs.
Impact for SARS-CoV2/COVID19 research efforts
Treatment of SARS-CoV2-infected individuals / COVID19 patients (repurposing known antivirals to treat SARS-CoV2).
In silico study / bioinformatics study
In vitro study
Strengths and limitations of the paper
Novelty: Four previously unreported and effective (in vitro) drugs identified as potential candidates for SARS-CoV2 treatment. Antibodies from sera from convalescent SARS-CoV2 patients used in the assay as shown to have higher sensitivity than commercially available antibodies.
Standing in the field:The drugs previously discovered to treat SARS-CoV2 infection are well summarised and are compared to the novel compounds.
Appropriate statistics: Not stated how many technical replicates were performed, statistics not described.
Viral model used:SARS-CoV-2/SP02/human/2020/BRA
Translatability:Identified drugs may be useful for repurposing/redesigning for the treatment of SARS-CoV2. The cellular network could be used to integrate other drugs currently in testing (e.g. remdesivir)
Main limitations: Replicates not stated, statistics not presented, cell line used may not be the most relevant for SARS-CoV2 infection, in vitro activity does not always translate into in vivo activity, why drugs applied before virus infection?