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Use of Human Lung Tissue Models for Screening of Drugs against SARS-CoV-2 Infection

Alexander J. McAuley, Petrus Jansen van Vuren, Muzaffar-Ur-Rehman Mohammed, Faheem, Sarah Goldie, Shane Riddell, Nathan J. Gödde, Ian K. Styles, Matthew P. Bruce, Simran Chahal, Stephanie Keating, Kim R. Blasdell, Mary Tachedjian, Carmel M. O’Brien, Nagendrakumar Balasubramanian Singanallur, John Noel Viana, Aditya V. Vashi, Carl M. Kirkpatrick, Christopher A. MacRaild, Rohan M. Shah, Elizabeth Vincan, Eugene Athan, Darren J. Creek, Natalie L. Trevaskis, Sankaranarayanan Murugesan, Anupama Kumar, and Seshadri S. Vasan
Abstract

The repurposing of licensed drugs for use against COVID-19 is one of the most rapid ways to develop new and alternative therapeutic options to manage the ongoing pandemic. Given circa 7817 licensed compounds available from Compounds Australia that can be screened, this paper demonstrates the utility of commercially available ex vivo/3D airway and alveolar tissue models. These models are a closer representation of in vivo studies than in vitro models, but retain the benefits of rapid in vitro screening for drug efficacy. We demonstrate that several existing drugs appear to show anti-SARS-CoV-2 activity against both SARS-CoV-2 Delta and Omicron Variants of Concern in the airway model. In particular, fluvoxamine, as well as aprepitant, everolimus, and sirolimus, has virus reduction efficacy comparable to the current standard of care (remdesivir, molnupiravir, nirmatrelvir). Whilst these results are encouraging, further testing and efficacy studies are required before clinical use can be considered.

Keywords

EpiAirway (AIR-100), EpiAlveolar (ALV-100-FT-PE12), COVID-19, SARS-CoV-2 delta variant, omicron variant, therapeutics, drug repurposing, anti-viral drug screening, remdesivir, molnupiravir, nirmatrelvir, aprepitant, cyclizine, cetirizine, everolimus, fluvoxamine, lapatinib, L-cycloserine, ondansetron, probenecid, pyrimethamine, rolapitant, sirolimus, virus titre, viral reproduction, TCID50 .

Materials Tested

remdesivir, molnupiravir, nirmatrelvir, aprepitant, cyclizine, cetirizine, everolimus, fluvoxamine, lapatinib, L-cycloserine, ondansetron, probenecid, pyrimethamine, rolapitant, sirolimus, DMSO

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