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

Author:

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

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 circa 7817 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 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.

Funder

Australian Department of Health through its Medical Research Future Fund

United States Food and Drug Administration (FDA) Medical Countermeasures Initiative

Publisher

MDPI AG

Subject

Virology,Infectious Diseases

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