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

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...

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Autores principales: McAuley, Alexander J., Jansen van Vuren, Petrus, Mohammed, Muzaffar-Ur-Rehman, Faheem, Goldie, Sarah, Riddell, Shane, Gödde, Nathan J., Styles, Ian K., Bruce, Matthew P., Chahal, Simran, Keating, Stephanie, Blasdell, Kim R., Tachedjian, Mary, O’Brien, Carmel M., Singanallur, Nagendrakumar Balasubramanian, Viana, John Noel, Vashi, Aditya V., Kirkpatrick, Carl M., MacRaild, Christopher A., Shah, Rohan M., Vincan, Elizabeth, Athan, Eugene, Creek, Darren J., Trevaskis, Natalie L., Murugesan, Sankaranarayanan, Kumar, Anupama, Vasan, Seshadri S.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9693925/
https://www.ncbi.nlm.nih.gov/pubmed/36366514
http://dx.doi.org/10.3390/v14112417
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author McAuley, Alexander J.
Jansen van Vuren, Petrus
Mohammed, Muzaffar-Ur-Rehman
Faheem,
Goldie, Sarah
Riddell, Shane
Gödde, Nathan J.
Styles, Ian K.
Bruce, Matthew P.
Chahal, Simran
Keating, Stephanie
Blasdell, Kim R.
Tachedjian, Mary
O’Brien, Carmel M.
Singanallur, Nagendrakumar Balasubramanian
Viana, John Noel
Vashi, Aditya V.
Kirkpatrick, Carl M.
MacRaild, Christopher A.
Shah, Rohan M.
Vincan, Elizabeth
Athan, Eugene
Creek, Darren J.
Trevaskis, Natalie L.
Murugesan, Sankaranarayanan
Kumar, Anupama
Vasan, Seshadri S.
author_facet McAuley, Alexander J.
Jansen van Vuren, Petrus
Mohammed, Muzaffar-Ur-Rehman
Faheem,
Goldie, Sarah
Riddell, Shane
Gödde, Nathan J.
Styles, Ian K.
Bruce, Matthew P.
Chahal, Simran
Keating, Stephanie
Blasdell, Kim R.
Tachedjian, Mary
O’Brien, Carmel M.
Singanallur, Nagendrakumar Balasubramanian
Viana, John Noel
Vashi, Aditya V.
Kirkpatrick, Carl M.
MacRaild, Christopher A.
Shah, Rohan M.
Vincan, Elizabeth
Athan, Eugene
Creek, Darren J.
Trevaskis, Natalie L.
Murugesan, Sankaranarayanan
Kumar, Anupama
Vasan, Seshadri S.
author_sort McAuley, Alexander J.
collection PubMed
description 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.
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spelling pubmed-96939252022-11-26 Use of Human Lung Tissue Models for Screening of Drugs against SARS-CoV-2 Infection McAuley, Alexander J. Jansen van Vuren, Petrus Mohammed, Muzaffar-Ur-Rehman Faheem, Goldie, Sarah Riddell, Shane Gödde, Nathan J. Styles, Ian K. Bruce, Matthew P. Chahal, Simran Keating, Stephanie Blasdell, Kim R. Tachedjian, Mary O’Brien, Carmel M. Singanallur, Nagendrakumar Balasubramanian Viana, John Noel Vashi, Aditya V. Kirkpatrick, Carl M. MacRaild, Christopher A. Shah, Rohan M. Vincan, Elizabeth Athan, Eugene Creek, Darren J. Trevaskis, Natalie L. Murugesan, Sankaranarayanan Kumar, Anupama Vasan, Seshadri S. Viruses Article 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. MDPI 2022-10-31 /pmc/articles/PMC9693925/ /pubmed/36366514 http://dx.doi.org/10.3390/v14112417 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
McAuley, Alexander J.
Jansen van Vuren, Petrus
Mohammed, Muzaffar-Ur-Rehman
Faheem,
Goldie, Sarah
Riddell, Shane
Gödde, Nathan J.
Styles, Ian K.
Bruce, Matthew P.
Chahal, Simran
Keating, Stephanie
Blasdell, Kim R.
Tachedjian, Mary
O’Brien, Carmel M.
Singanallur, Nagendrakumar Balasubramanian
Viana, John Noel
Vashi, Aditya V.
Kirkpatrick, Carl M.
MacRaild, Christopher A.
Shah, Rohan M.
Vincan, Elizabeth
Athan, Eugene
Creek, Darren J.
Trevaskis, Natalie L.
Murugesan, Sankaranarayanan
Kumar, Anupama
Vasan, Seshadri S.
Use of Human Lung Tissue Models for Screening of Drugs against SARS-CoV-2 Infection
title Use of Human Lung Tissue Models for Screening of Drugs against SARS-CoV-2 Infection
title_full Use of Human Lung Tissue Models for Screening of Drugs against SARS-CoV-2 Infection
title_fullStr Use of Human Lung Tissue Models for Screening of Drugs against SARS-CoV-2 Infection
title_full_unstemmed Use of Human Lung Tissue Models for Screening of Drugs against SARS-CoV-2 Infection
title_short Use of Human Lung Tissue Models for Screening of Drugs against SARS-CoV-2 Infection
title_sort use of human lung tissue models for screening of drugs against sars-cov-2 infection
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9693925/
https://www.ncbi.nlm.nih.gov/pubmed/36366514
http://dx.doi.org/10.3390/v14112417
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