https://scholars.lib.ntu.edu.tw/handle/123456789/553010
標題: | Enhancement of the IFN-β-induced host signature informs repurposed drugs for COVID-19 | 作者: | Huang, Chen-Tsung TAI-LING CHAO Kao, Han-Chieh Pang, Yu-Hao Lee, Wen-Hau Hsieh, Chiao-Hui SUI-YUAN CHANG Huang, Hsuan-Cheng Juan, H.-F. |
關鍵字: | Bioinformatics; COVID-19; Drug repurposing; Host-directed therapy; Infectious disease; Pharmaceutical science; Systems biology; Transcriptomics; Type I interferon | 公開日期: | 十二月-2020 | 卷: | 6 | 期: | 12 | 來源出版物: | Heliyon | 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. |
URI: | https://scholars.lib.ntu.edu.tw/handle/123456789/553010 | ISSN: | 2405-8440 | DOI: | 10.1016/j.heliyon.2020.e05646 |
顯示於: | 醫學檢驗暨生物技術學系 |
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