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; Seshadri S Vasan

doi:10.3390/v14112417

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

Viruses. 2022 Oct 31;14(11):2417. doi: 10.3390/v14112417.

Authors

Alexander J McAuley¹, Petrus Jansen van Vuren¹, Muzaffar-Ur-Rehman Mohammed², Faheem³, Sarah Goldie¹, Shane Riddell¹, Nathan J Gödde⁴, Ian K Styles⁵, Matthew P Bruce¹, Simran Chahal⁶, Stephanie Keating¹, Kim R Blasdell¹, Mary Tachedjian¹, Carmel M O'Brien^{7

8}, Nagendrakumar Balasubramanian Singanallur¹, John Noel Viana^{9

10}, Aditya V Vashi⁷, Carl M Kirkpatrick¹¹, Christopher A MacRaild⁵, Rohan M Shah¹², Elizabeth Vincan^{6

13}, Eugene Athan¹⁴, Darren J Creek⁵, Natalie L Trevaskis⁵, Sankaranarayanan Murugesan², Anupama Kumar¹⁵, Seshadri S Vasan^{1

16

17}

Affiliations

¹ Australian Centre for Disease Preparedness, Commonwealth Scientific and Industrial Research Organisation, Portarlington Road, Geelong, VIC 3220, Australia.
² Department of Pharmacy, Birla Institute of Technology and Science, Pilani 333031, India.
³ Department of Medicinal Chemistry, University of Utah, Salt Lake City, UT 84112, USA.
⁴ The Australian Institute for Bioengineering and Nanotechnology, The University of Queensland, Brisbane, QLD 4075, Australia.
⁵ Disposition and Dynamics, Monash Institute of Pharmaceutical Sciences, Monash University, Parkville, VIC 3052, Australia.
⁶ Victorian Infectious Diseases Reference Laboratory, Melbourne, VIC 3000, Australia.
⁷ Manufacturing, Commonwealth Scientific and Industrial Research Organisation, Research Way, Clayton, VIC 3168, Australia.
⁸ Australian Regenerative Medicine Institute, Monash University, Clayton, VIC 3168, Australia.
⁹ Australian National Centre for the Public Awareness of Science, Australian National University, Canberra, ACT 2601, Australia.
¹⁰ Responsible Innovation Future Science Platform, Commonwealth Scientific and Industrial Research Organisation, Boggo Road, Dutton Park, QLD 4102, Australia.
¹¹ Centre for Medicine Use and Safety, Monash Institute of Pharmaceutical Sciences, Monash University, Parkville, VIC 3052, Australia.
¹² Department of Chemistry and Biochemistry, Swinburne University of Technology, Hawthorn, VIC 3122, Australia.
¹³ Department of Infectious Diseases, University of Melbourne, Melbourne, VIC 3000, Australia.
¹⁴ School of Medicine, Deakin University, Pigdons Road, Waurn Ponds, VIC 3216, Australia.
¹⁵ Land & Water, Commonwealth Scientific and Industrial Research Organisation, Waite Campus, Urrbrae, SA 5064, Australia.
¹⁶ Department of Health, 189 Royal Street, East Perth, WA 6004, Australia.
¹⁷ Department of Health Sciences, University of York, York YO10 5DD, UK.

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.

Keywords: 3D tissue models; COVID-19; CoviRx.org; drug repurposing; therapeutics.

Publication types

Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, P.H.S.

MeSH terms

Antiviral Agents / pharmacology
Antiviral Agents / therapeutic use
COVID-19 Drug Treatment*
Humans
Lung
Pandemics
SARS-CoV-2*

Substances

Antiviral Agents

Supplementary concepts

SARS-CoV-2 variants

Grants and funding

This research was kindly funded (Principal Investigator: S.S.V.) by the Australian Department of Health through its Medical Research Future Fund (Grant Number MRF2009092) and the United States Food and Drug Administration (FDA) Medical Countermeasures Initiative (Contract Number 75F40121C00144). The article reflects the views of the authors and does not represent the views or policies of the funding agencies, including the FDA.