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

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. ShahElizabeth Vincan, Eugene Athan, Darren J. Creek, Natalie L. Trevaskis, Sankaranarayanan Murugesan, Anupama Kumar, Seshadri S. Vasan^*

^*Corresponding author for this work

School of Regulation & Global Governance

Research output: Contribution to journal › Article › peer-review

8 Citations (Scopus)

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.

Original language	English
Article number	2417
Number of pages	18
Journal	Viruses
Volume	14
Issue number	11
DOIs	https://doi.org/10.3390/v14112417
Publication status	Published - Nov 2022

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10.3390/v14112417Licence: CC BY

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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., ... Vasan, S. S. (2022). Use of Human Lung Tissue Models for Screening of Drugs against SARS-CoV-2 Infection. Viruses, 14(11), Article 2417. https://doi.org/10.3390/v14112417

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title = "Use of Human Lung Tissue Models for Screening of Drugs against SARS-CoV-2 Infection",

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",

author = "McAuley, \{Alexander J.\} and \{Jansen van Vuren\}, Petrus and Mohammed, \{Muzaffar Ur Rehman\} and Faheem and Sarah Goldie and Shane Riddell and G{\"o}dde, \{Nathan J.\} and Styles, \{Ian K.\} and Bruce, \{Matthew P.\} and Simran Chahal and Stephanie Keating and Blasdell, \{Kim R.\} and Mary Tachedjian and O{\textquoteright}Brien, \{Carmel M.\} and Singanallur, \{Nagendrakumar Balasubramanian\} and Viana, \{John Noel\} and Vashi, \{Aditya V.\} and Kirkpatrick, \{Carl M.\} and MacRaild, \{Christopher A.\} and Shah, \{Rohan M.\} and Elizabeth Vincan and Eugene Athan and Creek, \{Darren J.\} and Trevaskis, \{Natalie L.\} and Sankaranarayanan Murugesan and Anupama Kumar and Vasan, \{Seshadri S.\}",

note = "{\textcopyright} 2022 by the authors.",

year = "2022",

month = nov,

doi = "10.3390/v14112417",

language = "English",

volume = "14",

journal = "Viruses",

issn = "1999-4915",

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McAuley, AJ, Jansen van Vuren, P, Mohammed, MUR, Faheem, Goldie, S, Riddell, S, Gödde, NJ, Styles, IK, Bruce, MP, Chahal, S, Keating, S, Blasdell, KR, Tachedjian, M, O’Brien, CM, Singanallur, NB, Viana, JN, Vashi, AV, Kirkpatrick, CM, MacRaild, CA, Shah, RM, Vincan, E, Athan, E, Creek, DJ, Trevaskis, NL, Murugesan, S, Kumar, A & Vasan, SS 2022, 'Use of Human Lung Tissue Models for Screening of Drugs against SARS-CoV-2 Infection', Viruses, vol. 14, no. 11, 2417. https://doi.org/10.3390/v14112417

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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,

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.

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 - https://www.scopus.com/pages/publications/85141622756

U2 - 10.3390/v14112417

DO - 10.3390/v14112417

M3 - Article

SN - 1999-4915

VL - 14

JO - Viruses

JF - Viruses

IS - 11

M1 - 2417

ER -

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

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