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

Given the faithful recapitulation of human lung responses to influenza infection we had observed, we quickly pivoted our effort to focus on SARS-CoV-2 infection when we learned of the emerging COVID19 pandemic. To alleviate safety concerns and immediately initiate work in our BSL2 laboratory, we designed SARS-CoV-2 pseudoparticles (CoV-2pp) that contain the SARS-CoV-2 spike (S) protein assembled onto luciferase reporter gene-carrying retroviral core particles 20 , based on the genome sequence of SARS-CoV-2 released on January 12, 2020 21, 22 . We confirmed that the pseudovirions contained both full length (S1 + S2) and cleaved versions of the SARS-CoV-2 S protein as detected using Western blot analysis with an S1 antibody ( Fig. S5A ), as previously shown in other pseudotyped SARS-CoV-2 viruses 14,23 . These pseudotyped viral particles can faithfully reflect key aspects of native SARS-CoV-2 entry into host cells via binding to its ACE2 receptor 23 , and thus, they can be used to test potential entry inhibitors of SARS-CoV-2 14,20 . Vesicular stomatitis virus (VSV) GP protein pseudoparticles (VSVpp) were also generated and used in parallel studies to exclude toxic and non-specific effects of SARS-CoV-2 entry inhibitors 14,20 . Successful generation of SARS-CoV-2pp was confirmed by efficient infection of Huh-7 cells, a human liver cell line commonly used to study infection by SARS viruses 24 , whereas author/funder. All rights reserved. No reuse allowed without permission.