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Heliyon
. 2020 Dec;6(12):e05646.
doi: 10.1016/j.heliyon.2020.e05646. Epub 2020 Dec 2.
Enhancement of the IFN-β-induced host signature informs repurposed drugs for COVID-19
Chen-Tsung Huang 1 , Tai-Ling Chao 2 , Han-Chieh Kao 2 , Yu-Hao Pang 2 , Wen-Hau Lee 2 , Chiao-Hui Hsieh 3 , Sui-Yuan Chang 2 4 , Hsuan-Cheng Huang 5 , Hsueh-Fen Juan 1 3
Affiliations
- PMID: 33289002
- PMCID: PMC7709728
- DOI: 10.1016/j.heliyon.2020.e05646
Abstract
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a causative agent for the outbreak of coronavirus disease 2019 (COVID-19). This global pandemic is now calling for efforts to develop more effective COVID-19 therapies. Here we use a host-directed approach, which focuses on cellular responses to diverse small-molecule treatments, to identify potentially effective drugs for COVID-19. This framework looks at the ability of compounds to elicit a similar transcriptional response to IFN-β, a type I interferon that fails to be induced at notable levels in response to SARS-CoV-2 infection. By correlating the perturbation profiles of ~3,000 small molecules with a high-quality signature of IFN-β-responsive genes in primary normal human bronchial epithelial cells, our analysis revealed four candidate COVID-19 compounds, namely homoharringtonine, narciclasine, anisomycin, and emetine. We experimentally confirmed that the predicted compounds significantly inhibited SARS-CoV-2 replication in Vero E6 cells at nanomolar, relatively non-toxic concentrations, with half-maximal inhibitory concentrations of 165.7 nM, 16.5 nM, and 31.4 nM for homoharringtonine, narciclasine, and anisomycin, respectively. Together, our results corroborate a host-centric strategy to inform protective antiviral therapies for COVID-19.
Keywords: Bioinformatics; COVID-19; Drug repurposing; Host-directed therapy; Infectious disease; Pharmaceutical science; Systems biology; Transcriptomics; Type I interferon.