Artificial intelligence approach fighting COVID-19 with repurposing drugs

• Main Authors: Yi-Yu Ke, Tzu-Ting Peng, Teng-Kuang Yeh, Wen-Zheng Huang, Shao-En Chang, Szu-Huei Wu, Hui-Chen Hung, Tsu-An Hsu, Shiow-Ju Lee, Jeng-Shin Song, Wen-Hsing Lin, Tung-Jung Chiang, Jiunn-Horng Lin, Huey-Kang Sytwu, Chiung-Tong Chen
• Format: Article
• Language: English
• Published: Elsevier 2020-08-01
• Series: Biomedical Journal
• Subjects: AI; DNN; COVID-19; SARS-CoV-2; Feline coronavirus; Drug repurposing
• Online Access: http://www.sciencedirect.com/science/article/pii/S2319417020300494

Background: The ongoing COVID-19 pandemic has caused more than 193,825 deaths during the past few months. A quick-to-be-identified cure for the disease will be a therapeutic medicine that has prior use experiences in patients in order to resolve the current pandemic situation before it could become worsening. Artificial intelligence (AI) technology is hereby applied to identify the marketed drugs with potential for treating COVID-19. Methods: An AI platform was established to identify potential old drugs with anti-coronavirus activities by using two different learning databases; one consisted of the compounds reported or proven active against SARS-CoV, SARS-CoV-2, human immunodeficiency virus, influenza virus, and the other one containing the known 3C-like protease inhibitors. All AI predicted drugs were then tested for activities against a feline coronavirus in in vitro cell-based assay. These assay results were feedbacks to the AI system for relearning and thus to generate a modified AI model to search for old drugs again. Results: After a few runs of AI learning and prediction processes, the AI system identified 80 marketed drugs with potential. Among them, 8 drugs (bedaquiline, brequinar, celecoxib, clofazimine, conivaptan, gemcitabine, tolcapone, and vismodegib) showed in vitro activities against the proliferation of a feline infectious peritonitis (FIP) virus in Fcwf-4 cells. In addition, 5 other drugs (boceprevir, chloroquine, homoharringtonine, tilorone, and salinomycin) were also found active during the exercises of AI approaches. Conclusion: Having taken advantages of AI, we identified old drugs with activities against FIP coronavirus. Further studies are underway to demonstrate their activities against SARS-CoV-2 in vitro and in vivo at clinically achievable concentrations and doses. With prior use experiences in patients, these old drugs if proven active against SARS-CoV-2 can readily be applied for fighting COVID-19 pandemic.