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ColdZyme Maintains Integrity in SARS-CoV-2-Infected Airway Epithelia.
mBio. 2021 04 27; 12(2)MBIO

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.

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Authors+Show Affiliations

Posch W
Institute of Hygiene and Medical Microbiology, Medical University of Innsbruck, Innsbruck, Austria.
Vosper J
Institute of Medical Biochemistry, Geneva, Switzerland.
Zaderer V
Institute of Hygiene and Medical Microbiology, Medical University of Innsbruck, Innsbruck, Austria.
Noureen A
Institute of Hygiene and Medical Microbiology, Medical University of Innsbruck, Innsbruck, Austria.
Constant S
Epithelix Sàrl, Geneva, Switzerland.
Bellmann-Weiler R
University Hospital of Internal Medicine II, Medical University of Innsbruck, Innsbruck, Austria.
Lass-Flörl C
Institute of Hygiene and Medical Microbiology, Medical University of Innsbruck, Innsbruck, Austria cornelia.lass-floerl@i-med.ac.at doris.wilflingseder@i-med.ac.at.
Wilflingseder D
Institute of Hygiene and Medical Microbiology, Medical University of Innsbruck, Innsbruck, Austria cornelia.lass-floerl@i-med.ac.at doris.wilflingseder@i-med.ac.at.

MeSH

Antiviral AgentsBronchiCOVID-19Complement C3Epithelial CellsHumansImmunity, InnateNasal MucosaOral SpraysRespiratory MucosaSARS-CoV-2Virus Attachment

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

33906927

Citation

Posch, W, et al. "ColdZyme Maintains Integrity in SARS-CoV-2-Infected Airway Epithelia." MBio, vol. 12, no. 2, 2021.
Posch W, Vosper J, Zaderer V, et al. ColdZyme Maintains Integrity in SARS-CoV-2-Infected Airway Epithelia. mBio. 2021;12(2).
Posch, W., Vosper, J., Zaderer, V., Noureen, A., Constant, S., Bellmann-Weiler, R., Lass-Flörl, C., & Wilflingseder, D. (2021). ColdZyme Maintains Integrity in SARS-CoV-2-Infected Airway Epithelia. MBio, 12(2). https://doi.org/10.1128/mBio.00904-21
Posch W, et al. ColdZyme Maintains Integrity in SARS-CoV-2-Infected Airway Epithelia. mBio. 2021 04 27;12(2) PubMed PMID: 33906927.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - ColdZyme Maintains Integrity in SARS-CoV-2-Infected Airway Epithelia. AU - Posch,W, AU - Vosper,J, AU - Zaderer,V, AU - Noureen,A, AU - Constant,S, AU - Bellmann-Weiler,R, AU - Lass-Flörl,C, AU - Wilflingseder,D, Y1 - 2021/04/27/ PY - 2021/4/28/entrez PY - 2021/4/29/pubmed PY - 2021/5/12/medline KW - ColdZyme KW - SARS-CoV-2 KW - airway epithelia KW - anaphylatoxins KW - antiviral response JF - mBio JO - mBio VL - 12 IS - 2 N2 - 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. SN - 2150-7511 UR - https://www.unboundmedicine.com/medline/citation/33906927/ColdZyme_Maintains_Integrity_in_SARS_CoV_2_Infected_Airway_Epithelia_ DB - PRIME DP - Unbound Medicine ER -