期刊论文详细信息
Heliyon
Enhancement of the IFN-β-induced host signature informs repurposed drugs for COVID-19
Hsueh-Fen Juan1  Hsuan-Cheng Huang2  Sui-Yuan Chang3  Tai-Ling Chao3  Yu-Hao Pang3  Han-Chieh Kao3  Wen-Hau Lee3  Chiao-Hui Hsieh4  Chen-Tsung Huang5 
[1] Corresponding author.;Department of Laboratory Medicine, National Taiwan University Hospital, Taipei 10002, Taiwan;Department of Clinical Laboratory Sciences and Medical Biotechnology, National Taiwan University, Taipei 10048, Taiwan;Department of Life Science, National Taiwan University, Taipei 10617, Taiwan;Graduate Institute of Biomedical Electronics and Bioinformatics, National Taiwan University, Taipei 10617, Taiwan;
关键词: Systems biology;    COVID-19;    Host-directed therapy;    Type I interferon;    Drug repurposing;    Bioinformatics;   
DOI  :  
来源: DOAJ
【 摘 要 】

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.

【 授权许可】

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