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 the potential of using these drugs as COVID19 prophylactic therapies, we then pretreated the human Airway Chips by perfusing their vascular channel with chloroquine, arbidol, toremifene, clomiphene, amodiaquine, verapamil, or amiodarone at their maximum concentration (Cmax) in blood reported in humans ( Table 1) to mimic systemic distribution after oral administration for 24 hours, before adding the CoV-2pp into the airway channel, and then continuously flowing the drug through the vascular channel for 48 additional hours. These studies revealed that only two of these drugs  amodiaquine and toremiphene  displayed statistically significant inhibition of viral infection under these more clinically relevant experimental conditions (Fig. 4B) . The finding that arbidol did not significantly inhibit the entry of CoV-2pp in the human Airway