TY - JOUR
T1 - Use of Human Lung Tissue Models for Screening of Drugs against SARS-CoV-2 Infection
AU - McAuley, Alexander J.
AU - Jansen van Vuren, Petrus
AU - Mohammed, Muzaffar Ur Rehman
AU - Faheem, null
AU - Goldie, Sarah
AU - Riddell, Shane
AU - Gödde, Nathan J.
AU - Styles, Ian K.
AU - Bruce, Matthew P.
AU - Chahal, Simran
AU - Keating, Stephanie
AU - Blasdell, Kim R.
AU - Tachedjian, Mary
AU - O’Brien, Carmel M.
AU - Singanallur, Nagendrakumar Balasubramanian
AU - Viana, John Noel
AU - Vashi, Aditya V.
AU - Kirkpatrick, Carl M.
AU - MacRaild, Christopher A.
AU - Shah, Rohan M.
AU - Vincan, Elizabeth
AU - Athan, Eugene
AU - Creek, Darren J.
AU - Trevaskis, Natalie L.
AU - Murugesan, Sankaranarayanan
AU - Kumar, Anupama
AU - Vasan, Seshadri S.
N1 - Funding Information:
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.
Publisher Copyright:
© 2022 by the authors.
PY - 2022/11
Y1 - 2022/11
N2 - 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.
AB - 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.
KW - 3D tissue models
KW - COVID-19
KW - CoviRx.org
KW - drug repurposing
KW - therapeutics
UR - http://www.scopus.com/inward/record.url?scp=85141622756&partnerID=8YFLogxK
U2 - 10.3390/v14112417
DO - 10.3390/v14112417
M3 - Article
C2 - 36366514
AN - SCOPUS:85141622756
SN - 1999-4915
VL - 14
JO - Viruses
JF - Viruses
IS - 11
M1 - 2417
ER -
