Enhancement of the IFN-β-induced host signature informs repurposed drugs for COVID-19

  • Heliyon. 2020 Dec;6(12):e05646. doi: 10.1016/j.heliyon.2020.e05646.
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
  • 1. Graduate Institute of Biomedical Electronics and Bioinformatics, National Taiwan University, Taipei 10617, Taiwan.
  • 2. Department of Clinical Laboratory Sciences and Medical Biotechnology, National Taiwan University, Taipei 10048, Taiwan.
  • 3. Department of Life Science, National Taiwan University, Taipei 10617, Taiwan.
  • 4. Department of Laboratory Medicine, National Taiwan University Hospital, Taipei 10002, Taiwan.
  • 5. Institute of Biomedical Informatics, National Yang-Ming University, Taipei 11221, Taiwan.
PMID: 33289002 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.
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