ColdZyme Maintains Integrity in SARS-CoV-2-Infected Airway Epithelia

ABSTRACT SARS-CoV-2 infection causing the COVID-19 pandemic calls for immediate interventions to avoid viral transmission, disease progression, and subsequent excessive inflammation and tissue destruction. Primary normal human bronchial epithelial cells are among the first targets of SARS-CoV-2 infe...

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Autores principales:	W. Posch, J. Vosper, V. Zaderer, A. Noureen, S. Constant, R. Bellmann-Weiler, C. Lass-Flörl, D. Wilflingseder
Formato:	article
Lenguaje:	EN
Publicado:	American Society for Microbiology 2021
Materias:	ColdZyme SARS-CoV-2 airway epithelia anaphylatoxins antiviral response Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/5d59a8b61eb8401bb6d831102cd74afd
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spelling	oai:doaj.org-article:5d59a8b61eb8401bb6d831102cd74afd2021-11-10T18:37:48ZColdZyme Maintains Integrity in SARS-CoV-2-Infected Airway Epithelia10.1128/mBio.00904-212150-7511https://doaj.org/article/5d59a8b61eb8401bb6d831102cd74afd2021-04-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mBio.00904-21https://doaj.org/toc/2150-7511ABSTRACT SARS-CoV-2 infection causing the COVID-19 pandemic calls for immediate interventions to avoid viral transmission, disease progression, and subsequent excessive inflammation and tissue destruction. Primary normal human bronchial epithelial cells are among the first targets of SARS-CoV-2 infection. Here, we show that ColdZyme medical device mouth spray efficiently protected against virus entry, excessive inflammation, and tissue damage. Applying ColdZyme to fully differentiated, polarized human epithelium cultured at an air-liquid interphase (ALI) completely blocked binding of SARS-CoV-2 and increased local complement activation mediated by the virus as well as productive infection of the tissue model. While SARS-CoV-2 infection resulted in exaggerated intracellular complement activation immediately following infection and a drop in transepithelial resistance, these parameters were bypassed by single pretreatment of the tissues with ColdZyme mouth spray. Crucially, our study highlights the importance of testing already evaluated and safe drugs such as ColdZyme mouth spray for maintaining epithelial integrity and hindering SARS-CoV-2 entry within standardized three-dimensional (3D) in vitro models mimicking the in vivo human airway epithelium. IMPORTANCE Although our understanding of COVID-19 continuously progresses, essential questions regarding prophylaxis and treatment remain open. A hallmark of severe SARS-CoV-2 infection is a hitherto-undescribed mechanism leading to excessive inflammation and tissue destruction associated with enhanced pathogenicity and mortality. To tackle the problem at the source, transfer of SARS-CoV-2, subsequent binding, infection, and inflammatory responses have to be avoided. In this study, we used fully differentiated, mucus-producing, and ciliated human airway epithelial cultures to test the efficacy of ColdZyme medical device mouth spray in terms of protection from SARS-CoV-2 infection. Importantly, we found that pretreatment of the in vitro airway cultures using ColdZyme mouth spray resulted in significantly shielding the epithelial integrity, hindering virus binding and infection, and blocking excessive intrinsic complement activation within the airway cultures. Our in vitro data suggest that ColdZyme mouth spray may have an impact in prevention of COVID-19.W. PoschJ. VosperV. ZadererA. NoureenS. ConstantR. Bellmann-WeilerC. Lass-FlörlD. WilflingsederAmerican Society for MicrobiologyarticleColdZymeSARS-CoV-2airway epitheliaanaphylatoxinsantiviral responseMicrobiologyQR1-502ENmBio, Vol 12, Iss 2 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	ColdZyme SARS-CoV-2 airway epithelia anaphylatoxins antiviral response Microbiology QR1-502
spellingShingle	ColdZyme SARS-CoV-2 airway epithelia anaphylatoxins antiviral response Microbiology QR1-502 W. Posch J. Vosper V. Zaderer A. Noureen S. Constant R. Bellmann-Weiler C. Lass-Flörl D. Wilflingseder ColdZyme Maintains Integrity in SARS-CoV-2-Infected Airway Epithelia
description	ABSTRACT SARS-CoV-2 infection causing the COVID-19 pandemic calls for immediate interventions to avoid viral transmission, disease progression, and subsequent excessive inflammation and tissue destruction. Primary normal human bronchial epithelial cells are among the first targets of SARS-CoV-2 infection. Here, we show that ColdZyme medical device mouth spray efficiently protected against virus entry, excessive inflammation, and tissue damage. Applying ColdZyme to fully differentiated, polarized human epithelium cultured at an air-liquid interphase (ALI) completely blocked binding of SARS-CoV-2 and increased local complement activation mediated by the virus as well as productive infection of the tissue model. While SARS-CoV-2 infection resulted in exaggerated intracellular complement activation immediately following infection and a drop in transepithelial resistance, these parameters were bypassed by single pretreatment of the tissues with ColdZyme mouth spray. Crucially, our study highlights the importance of testing already evaluated and safe drugs such as ColdZyme mouth spray for maintaining epithelial integrity and hindering SARS-CoV-2 entry within standardized three-dimensional (3D) in vitro models mimicking the in vivo human airway epithelium. IMPORTANCE Although our understanding of COVID-19 continuously progresses, essential questions regarding prophylaxis and treatment remain open. A hallmark of severe SARS-CoV-2 infection is a hitherto-undescribed mechanism leading to excessive inflammation and tissue destruction associated with enhanced pathogenicity and mortality. To tackle the problem at the source, transfer of SARS-CoV-2, subsequent binding, infection, and inflammatory responses have to be avoided. In this study, we used fully differentiated, mucus-producing, and ciliated human airway epithelial cultures to test the efficacy of ColdZyme medical device mouth spray in terms of protection from SARS-CoV-2 infection. Importantly, we found that pretreatment of the in vitro airway cultures using ColdZyme mouth spray resulted in significantly shielding the epithelial integrity, hindering virus binding and infection, and blocking excessive intrinsic complement activation within the airway cultures. Our in vitro data suggest that ColdZyme mouth spray may have an impact in prevention of COVID-19.
format	article
author	W. Posch J. Vosper V. Zaderer A. Noureen S. Constant R. Bellmann-Weiler C. Lass-Flörl D. Wilflingseder
author_facet	W. Posch J. Vosper V. Zaderer A. Noureen S. Constant R. Bellmann-Weiler C. Lass-Flörl D. Wilflingseder
author_sort	W. Posch
title	ColdZyme Maintains Integrity in SARS-CoV-2-Infected Airway Epithelia
title_short	ColdZyme Maintains Integrity in SARS-CoV-2-Infected Airway Epithelia
title_full	ColdZyme Maintains Integrity in SARS-CoV-2-Infected Airway Epithelia
title_fullStr	ColdZyme Maintains Integrity in SARS-CoV-2-Infected Airway Epithelia
title_full_unstemmed	ColdZyme Maintains Integrity in SARS-CoV-2-Infected Airway Epithelia
title_sort	coldzyme maintains integrity in sars-cov-2-infected airway epithelia
publisher	American Society for Microbiology
publishDate	2021
url	https://doaj.org/article/5d59a8b61eb8401bb6d831102cd74afd
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ColdZyme Maintains Integrity in SARS-CoV-2-Infected Airway Epithelia

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