Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

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

Version 1 : Received: 19 September 2022 / Approved: 20 September 2022 / Online: 20 September 2022 (03:24:22 CEST)

How to cite: McAuley, A.J.; Jansen van Vuren, P.; Mohammed, M.; Faheem, F.; 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. Preprints 2022, 2022090288 (doi: 10.20944/preprints202209.0288.v1). McAuley, A.J.; Jansen van Vuren, P.; Mohammed, M.; Faheem, F.; 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. Preprints 2022, 2022090288 (doi: 10.20944/preprints202209.0288.v1).

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.

Keywords

COVID-19; Therapeutics; Drug Repurposing; 3D Tissue Models

Subject

LIFE SCIENCES, Virology

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