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

Posch, Wilfried; Vosper, Jonathan; Zaderer, Viktoria; Noureen, Asma; Constant, Samuel; Bellmann‐Weiler, Rosa; Lass‐Flörl, Cornelia; Wilflingseder, Doris

doi:10.1128/mbio.00904-21

Cited by 15 publications

(28 citation statements)

References 32 publications

(51 reference statements)

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“…As recently shown, ColdZyme® mouth spray effectively blocked binding, uptake and infection of SARS-CoV-2 wildtype in a human respiratory model that was associated with rescue to tissue integrity and from excessive innate immune activation [ 9 ]. ColdZyme® is a Class III medical device (CE-marked) composed of glycerol, water, buffer, CaCl2, menthol and trypsin from the Atlantic cod ( Gadus morhua ) [ 10 ] (ClinicalTrials.gov, ID: NCT03901846).…”

Section: Introductionmentioning

confidence: 99%

“…Beside rhinovirus, RSV and influenza, SARS-CoV-2 as well as the common cold coronavirus HCoV-229E were demonstrated to be sensitive to prophylactic treatment with ColdZyme® mouth spray in previous in vitro analyses within various cellular systems, i.e. Vero E6 and MRC-5 cells, but also in 3D human airway epithelial tissue cultures [ 9 , 13 ]. Posch et al recently showed a robust engagement of complement in human airway epithelial (HAE) tissue cultures after viral infection, which was associated with high anaphylatoxin and pro-inflammatory cytokine release, high viral loads and excessive tissue destruction [ 9 , 13 ].…”

Section: Introductionmentioning

confidence: 99%

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ColdZyme® protects airway epithelia from infection with BA.4/5

et al. 2022

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Vaccines against SARS-CoV-2 protect from critical or severe pathogenesis also against new variants of concern (VOCs) such as BA.4 and BA.5, but immediate interventions to avoid viral transmission and subsequent inflammatory reactions are needed. Here we applied the ColdZyme® medical device mouth spray to fully differentiated, polarized human epithelium cultured at an air-liquid interphase (ALI). We found using VOCs BA.1 and BA.4/5 that this device effectively blocked respiratory tissue infection. While infection with these VOCs resulted in intracellular complement activation, thus enhanced inflammation, and drop of transepithelial resistance, these phenomena were prevented by a single administration of this medical device. Thus, ColdZyme® mouth spray significantly shields epithelial integrity, hinders virus infection and blocks in a secondary effect intrinsic complement activation within airway cultures also in terms of the highly contagious VOCs BA.4/5. Crucially, our in vitro data suggest that ColdZyme® mouth spray may have an impact to protect against SARS-CoV-2 transmission, also in case of the Omicron BA.1, BA.4 and BA.5 variants.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

ColdZyme® protects airway epithelia from infection with BA.4/5

et al. 2022

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“…Of course, the in vitro data are just a first step in a number of future testing—obviously, mucosal distribution, concentration, achieving a sufficiently high concentration of P80 in target cells and retention are critical parameters. As applying the P80 natural essence directly at mucosal surfaces to target DCs and LCs, the concentrations used in our in vitro setting with a range of 0.5 to 1% might be achieved in an in vivo scenario, but this needs further confirmation in an in vitro 3D mucosal tissue [ 28 , 29 ] and—If effective in murine models.…”

Section: Discussionmentioning

confidence: 99%

P80 Natural Essence Exerts Efficient Anti-HIV-1- as Well as Adjuvant Effects in DCs

et al. 2021

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Dendritic cells (DCs), as well as complement, play a major role during human immunodeficiency virus 1 (HIV-1) entry and infection at mucosal sites. Together, DCs and complement are key points for understanding host defence against HIV-1 infection and for studying the impact of new drugs on the regulation of innate host-pathogen interactions and adaptive immunity. For this, we evaluated the antiviral effect of the P80 natural essence (Longan extract) on interactions of non- and complement-opsonized HIV-1 with DCs. In viability assays, we first illustrated the effects of P80 natural essence on DC function. We found that P80 concentrations above 1.5% caused increased cell death, while at concentrations between 0.5% and 1% the compound exerted efficient antiviral effects in DCs and illustrated an adjuvant effect regarding DC activation. DC maturation, as well as co-stimulatory capacity, were significantly improved by P80 natural essence via p38 MAPK phosphorylation in presence of the viral challenge independent of the opsonization pattern. These findings might be exploited for future therapeutic options to target DC subsets directly at mucosal sites by P80 natural essence and to block entry of both, non- and complement-opsonized HIV-1.

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“…Augmenting this physical barrier with a topical spray has been suggested as one approach to reduce viral uptake. This concept is supported by in vitro data showing a reduction in SARS-CoV-2 binding to human airway epithelial cells after pre-treatment with a protease-containing glycerin barrier spray [ 5 ]; however, data confirming its efficacy in clinical trials is lacking.…”

Section: Viral Uptake and Local Upper Airway Mucosal Responsementioning

confidence: 97%