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

We then used the Huh-7 cell model in a 96 well format to test the effects of multiple drugs that have been approved by the FDA for other medical applications, including chloroquine, arbidol, toremifene, clomiphene, amodiaquine, verapamil, and amiodarone. These drugs were chosen based on the hypothesis that they might have broad-spectrum antiviral activity because they have been shown to inhibit infection by other viruses, such as influenza, SARS, or Ebola 25-27 . All of these drugs demonstrated dose-dependent inhibition of SARS-CoV-2pp entry in Huh-7 cells when added at 1 and 5 µM simultaneously with the virus and culturing for 72 hours (Fig. 4A) , without producing any detectable cell toxicity in this model (Fig. S6) . These results were promising, however, the Huh-7 cells were derived from a human liver tumor, whereas SARS-CoV-2 preferentially targets the lung in humans, and while this established cell line expresses low levels of ACE2 28 ; it does not express TMPRSS2 24,29 ; thus, the clinical relevance of these findings is not clear.