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

The copyright holder for this preprint (which was not peer-reviewed) is the . https://doi.org/10.1101/2020.04.13.039917 doi: bioRxiv preprint functional lung epithelium, they do not allow culturing at an air-liquid interface (ALI) or modeling of other physiologically relevant organ-level features of lung, such as mucus layer formation, mucociliary clearance, cross-talk between epithelium and endothelium, or recruitment of circulating immune cells 9,10 , all of which play key roles in host responses to infection by respiratory viruses. Moreover, in all of these culture models, drug studies are carried out under static conditions that cannot predict human responses to clinically relevant, dynamic drug exposure (PK) profiles. Importantly, while animal models are currently used as the benchmark for validation of therapeutics, they are not natural hosts for influenza virus or SARS-CoV-2, and when infection is possible, they commonly exhibit different systemic clinical manifestations from humans; husbandry requirements are also complex and expensive, and the ethics of using of non-human primates is garnering increasing concern even by NIH 12 . Thus, there is an urgent need for alternative preclinical models that better mimic human lung responses to infection by potential pandemic respiratory viruses, and because of their ability to recapitulate human organ-level physiology and pathophysiology, human Lung Chips offer a potential solution.