Enhancement of the IFN-β-induced host signature informs repurposed drugs for COVID-19
Journal
Heliyon
Journal Volume
6
Journal Issue
12
Date Issued
2020-12
Author(s)
Huang, Chen-Tsung
Kao, Han-Chieh
Pang, Yu-Hao
Lee, Wen-Hau
Hsieh, Chiao-Hui
Huang, Hsuan-Cheng
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.
Subjects
Bioinformatics; COVID-19; Drug repurposing; Host-directed therapy; Infectious disease; Pharmaceutical science; Systems biology; Transcriptomics; Type I interferon
SDGs
Type
journal article