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 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; Seshadri S Vasan

doi:10.20944/preprints202209.0288.v1

A peer-reviewed article of this Preprint also exists.

McAuley, A.J.; Jansen van Vuren, P.; Mohammed, M.-U.-R.; Faheem; Goldie, S.; Riddell, S.; Gödde, N.J.; Styles, I.K.; Bruce, M.P.; Chahal, S.; Keating, S.; Blasdell, K.R.; Tachedjian, M.; O’Brien, C.M.; Singanallur, N.B.; Viana, J.N.; Vashi, A.V.; Kirkpatrick, C.M.; MacRaild, C.A.; Shah, R.M.; Vincan, E.; Athan, E.; Creek, D.J.; Trevaskis, N.L.; Murugesan, S.; Kumar, A.; Vasan, S.S. Use of Human Lung Tissue Models for Screening of Drugs against SARS-CoV-2 Infection. Viruses 2022, 14, 2417. McAuley, A.J.; Jansen van Vuren, P.; Mohammed, M.-U.-R.; Faheem; Goldie, S.; Riddell, S.; Gödde, N.J.; Styles, I.K.; Bruce, M.P.; Chahal, S.; Keating, S.; Blasdell, K.R.; Tachedjian, M.; O’Brien, C.M.; Singanallur, N.B.; Viana, J.N.; Vashi, A.V.; Kirkpatrick, C.M.; MacRaild, C.A.; Shah, R.M.; Vincan, E.; Athan, E.; Creek, D.J.; Trevaskis, N.L.; Murugesan, S.; Kumar, A.; Vasan, S.S. Use of Human Lung Tissue Models for Screening of Drugs against SARS-CoV-2 Infection. Viruses 2022, 14, 2417.

Abstract

The repurposing of licenced 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 the approximately 8,000 licenced 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 compared to 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 Delta and Omicron Variants of Concern in the airway model. In particular, fluvoxamine, as well as aprepitant, everolimus, and sirolimus have 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.

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Copyright: This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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

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