Human organs-on-chips as tools for repurposing approved drugs as potential influenza and COVID19 therapeutics in viral pandemics

Longlong Si; Haiqing Bai; Melissa Rodas; Wuji Cao; Crystal Yur Oh; Amanda Jiang; Atiq Nurani; Danni Y Zhu; Girija Goyal; Sarah Gilpin; Rachelle Prantil-Baun; Donald E. Ingber

To explore whether the Airway Chip can be used to evaluate the efficacy of potential antiviral therapeutics, we firstly tested oseltamivir (Tamiflu), which is the antiinfluenza drug used most widely in the clinic. As oseltamivir is metabolized by the liver to release oseltamivir acid in vivo, we introduced this active metabolite into the vascular channel of Airway Chip infected with H1N1 virus, mimicking its blood levels after oral administration. Oseltamivir (1 µM) efficiently inhibited influenza replication (Fig. 3A) , prevented virus-induced compromise of barrier function (Fig. 3B) and disruption of epithelial tight junctions (Fig. 3C) , and decreased production of multiple cytokines and chemokines on-chip (Fig. 3D) . Thus, the Airway Chip faithfully replicates the effects of author/funder. All rights reserved. No reuse allowed without permission.