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Article ; Online: Correction: ColdZyme® protects airway epithelia from infection with BA.4/5.

Zaderer, Viktoria / Dichtl, Stefanie / Bellmann-Weiler, Rosa / Lass-Flörl, Cornelia / Posch, Wilfried / Wilflingseder, Doris

Respiratory research

2023 Volume 24, Issue 1, Page(s) 27

Language	English
Publishing date	2023-01-24
Publishing country	England
Document type	Published Erratum
ZDB-ID	2041675-1
ISSN	1465-993X ; 1465-993X
ISSN (online)	1465-993X
ISSN	1465-993X
DOI	10.1186/s12931-023-02326-4
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: P80 natural essence spray and lozenges provide respiratory protection against Influenza A, B, and SARS-CoV-2.

Zaderer, Viktoria / Diem, Gabriel / Posch, Wilfried / Jakschitz, Thomas / Bonn, Günther K / Bellmann-Weiler, Rosa / Huber, Lukas A / Wilflingseder, Doris

Respiratory research

2024 Volume 25, Issue 1, Page(s) 102

Abstract: Seasonally circulating viruses, such as Influenza, as well as newly emerging viruses and variants thereof, and waning immunity urge the need for safe, easy-to-use and inexpensive drugs to protect from these challenges. To prevent transmission of these ... ...

Abstract	Seasonally circulating viruses, such as Influenza, as well as newly emerging viruses and variants thereof, and waning immunity urge the need for safe, easy-to-use and inexpensive drugs to protect from these challenges. To prevent transmission of these viruses and subsequent excessive inflammatory reactions on mucous membranes, we tested the efficacy of the natural essence P80 as spray and in form of lozenges against respiratory infections caused by SARS-CoV-2 variants of concern (VoCs), influenza A (H3N2) and influenza B (Victoria). P80 natural essence, a Dimocarpus longan extract, shielded highly differentiated human airway epithelia from SARS-CoV-2 wildtype and Omicron variant as well as Influenza A and B infection and dampened inflammation by down-modulating pro-inflammatory cytokine and anaphylatoxin secretion. A single application of P80 natural essence spray maintained tissue integrity long-term. This also significantly reduced the release of infectious viral particles and the secretion of IP10, MCP1, RANTES and C3a, all of which mediate the migration of immune cells to the sites of infection. Even P80 lozenges dissolved in distilled water or non-neutralizing saliva efficiently prevented SARS-CoV-2 and Influenza-induced tissue destruction. Consequently, our in vitro data suggest that P80 natural essence can act as antiviral prophylactic, both in form of nasal or oral spray and in form of lozenges, independent of circulating respiratory challenges.
MeSH term(s)	Humans ; Influenza, Human/prevention & control ; Influenza A Virus, H3N2 Subtype ; SARS-CoV-2 ; COVID-19 ; Inflammation
Language	English
Publishing date	2024-02-28
Publishing country	England
Document type	Journal Article
ZDB-ID	2041675-1
ISSN	1465-993X ; 1465-993X
ISSN (online)	1465-993X
ISSN	1465-993X
DOI	10.1186/s12931-024-02718-0
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Article ; Online: ColdZyme® protects airway epithelia from infection with BA.4/5.

Zaderer, Viktoria / Dichtl, Stefanie / Bellmann Weiler, Rosa / Lass Flörl, Cornelia / Posch, Wilfried / Wilflingseder, Doris

Respiratory research

2022 Volume 23, Issue 1, Page(s) 300

Abstract: 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 ... ...

Abstract	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.
MeSH term(s)	Humans ; Epithelial Cells ; COVID-19 Vaccines ; SARS-CoV-2 ; COVID-19 ; Epithelium ; Respiratory Tract Infections/prevention & control
Chemical Substances	COVID-19 Vaccines
Language	English
Publishing date	2022-10-31
Publishing country	England
Document type	Letter
ZDB-ID	2041675-1
ISSN	1465-993X ; 1465-993X
ISSN (online)	1465-993X
ISSN	1465-993X
DOI	10.1186/s12931-022-02223-2
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Article ; Online: GlyPerA™ effectively shields airway epithelia from SARS-CoV-2 infection and inflammatory events.

Zaderer, Viktoria / Dichtl, Stefanie / Posch, Wilfried / Abiatari, Ivane / Bonn, Günther K / Jakschitz, Thomas / Huber, Lukas A / Kurzchalia, Teymuras V / Wilflingseder, Doris

Respiratory research

2023 Volume 24, Issue 1, Page(s) 88

Abstract: New SARS-CoV-2 variants of concern (VOCs) and waning immunity illustrate that quick and easy-to-use agents are needed to prevent infection. To protect from viral transmission and subsequent inflammatory reactions, we applied GlyperA™, a novel ... ...

Abstract	New SARS-CoV-2 variants of concern (VOCs) and waning immunity illustrate that quick and easy-to-use agents are needed to prevent infection. To protect from viral transmission and subsequent inflammatory reactions, we applied GlyperA™, a novel antimicrobial formulation that can be used as mouth gargling solution or as nasal spray, to highly differentiated human airway epithelia prior infection with Omicron VOCs BA.1 and BA.2. This formulation fully protected polarized human epithelium cultured in air-liquid interphase (ALI) from SARS-CoV-2-mediated tissue destruction and infection upon single application up to two days post infection. Moreover, inflammatory reactions induced by the Omicron VOCs were significantly lowered in tissue equivalents either pre-treated with the GlyperA™ solution, or even when added simultaneously. Thus, the GlyperA™ formulation significantly shielded epithelial integrity, successfully blocked infection with Omicron and release of viral particles, and decreased intracellular complement C3 activation within human airway epithelial cell cultures. Crucially, our in vitro data imply that GlyperA™ may be a simple tool to prevent from SARS-CoV-2 infection independent on the circulating variant via both, mouth and nose.
MeSH term(s)	Humans ; COVID-19 ; SARS-CoV-2 ; Epithelium ; Nose ; Inflammation
Language	English
Publishing date	2023-03-22
Publishing country	England
Document type	Letter
ZDB-ID	2041675-1
ISSN	1465-993X ; 1465-993X
ISSN (online)	1465-993X
ISSN	1465-993X
DOI	10.1186/s12931-023-02397-3
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Article ; Online: Omicron subvariants illustrate reduced respiratory tissue penetration, cell damage and inflammatory responses in human airway epithelia.

Zaderer, Viktoria / Abd El Halim, Hussam / Wyremblewsky, Anna-Lena / Lupoli, Gaia / Dächert, Christopher / Muenchhoff, Maximilian / Graf, Alexander / Blum, Helmut / Lass-Flörl, Cornelia / Keppler, Oliver T / Huber, Lukas A / Posch, Wilfried / Wilflingseder, Doris

Frontiers in immunology

2023 Volume 14, Page(s) 1258268

Abstract: Introduction: To explore whether the reported lower pathogenicity in infected individuals of variant of concern (VoC) Omicron and its current subvariants compared to VoC Delta may be related to fundamental differences in the initial virus-tissue ... ...

Abstract	Introduction: To explore whether the reported lower pathogenicity in infected individuals of variant of concern (VoC) Omicron and its current subvariants compared to VoC Delta may be related to fundamental differences in the initial virus-tissue interaction, we assessed their ability to penetrate, replicate and cause damage in a human 3D respiratory model. Methods: For this, we used TEER measurements, real-time PCR, LDH, cytokine and complex confocal imaging analyses. Results and discussion: We observed that Delta readily penetrated deep into the respiratory epithelium and this was associated with major tissue destruction, high LDH activity, high viral loads and pronounced innate immune activation as observed by intrinsic C3 activation and IL-6 release at infection sites. In contrast, Omicron subvariants BA.5, BQ.1.1 and BF7 remained superficially in the mucosal layer resulting merely in outward-directed destruction of cells, maintenance of epithelial integrity, minimal LDH activity and low basolateral release of virus at infection sites, as well as significantly smaller areas of complement activation and lower IL-6 secretion. Interestingly, also within Omicron subvariants differences were observed with newer Omicron subvariants BQ.1.1 and BF.7 illustrating significantly reduced viral loads, IL-6 release and LDH activity compared to BA.5. Our data indicate that earliest interaction events after SARS-CoV-2 transmission may have a role in shaping disease severity.
MeSH term(s)	Humans ; Interleukin-6 ; Respiratory Insufficiency ; Epithelium ; Respiratory Mucosa ; Complement Activation
Chemical Substances	Interleukin-6
Language	English
Publishing date	2023-10-17
Publishing country	Switzerland
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2606827-8
ISSN	1664-3224 ; 1664-3224
ISSN (online)	1664-3224
ISSN	1664-3224
DOI	10.3389/fimmu.2023.1258268
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Article ; Online: Salivary antibodies induced by BA.4/BA.5-convalescence or bivalent booster Immunoglobulin vaccination protect against novel SARS-COV-2 variants of concern.

Diem, Gabriel / Dichtl, Stefanie / Zaderer, Viktoria / Lass-Flörl, Cornelia / Reindl, Markus / Lupoli, Gaia / Dächert, Christopher / Muenchhoff, Maximilian / Graf, Alexander / Blum, Helmut / Keppler, Oliver T / Wilflingseder, Doris / Posch, Wilfried

Microbiology spectrum

2023 , Page(s) e0179323

Abstract: Currently, SARS-CoV-2 Omicron BA.5 subvariants BF.7 and BQ.1.1 are rapidly emerging worldwide. To evaluate the SARS-CoV-2-neutralizing capacity of sera and saliva from triple vaccinated individuals, either boosted with an adapted bivalent COVID-19 ... ...

Abstract	Currently, SARS-CoV-2 Omicron BA.5 subvariants BF.7 and BQ.1.1 are rapidly emerging worldwide. To evaluate the SARS-CoV-2-neutralizing capacity of sera and saliva from triple vaccinated individuals, either boosted with an adapted bivalent COVID-19 vaccine or recovered from BA.4/BA.5 infection, we analyzed the sensitivity of replication-competent SARS-CoV-2 Omicron subvariants BA.4/5, BQ.1.1 and BF.7 to neutralization. Analysis of SARS-CoV-2-specific IgGs and IgAs showed increased serum IgG titers in the vaccinated group, while the serum and salivary IgA levels were comparable. Similar and efficient serum neutralization against the ancestral strain of SARS-CoV-2 and Omicron BA.4/BA.5 was detected in both cohorts, but critically reduced for BQ.1.1 and BF.7. In contrast, salivary neutralization against BA.4/BA.5 was increased in the convalescent compared to the vaccinated group, while salivary neutralizing capacity against BQ.1.1 and BF.7 was comparable in these groups. Further, personalized protective effects studied in a human 3D respiratory model revealed the importance of salivary protection against different Omicron subvariants. IMPORTANCE In BA.4/BA.5-convalescent versus vaccinated groups, salivary neutralization capacity increased against SARS-CoV-2 Omicron BA.4/BA.5. In contrast, it neutralized novel Omicron subvariants BQ.1.1 and BF.7 similarly. Salivary protection against various Omicron subvariants was even more evident when tested in a personalized approach using highly differentiated respiratory human 3D models.
Language	English
Publishing date	2023-08-08
Publishing country	United States
Document type	Journal Article
ZDB-ID	2807133-5
ISSN	2165-0497 ; 2165-0497
ISSN (online)	2165-0497
ISSN	2165-0497
DOI	10.1128/spectrum.01793-23
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Article ; Online: Antiviral drugs block replication of highly immune-evasive Omicron subvariants ex vivo, but fail to reduce tissue inflammation.

Dichtl, Stefanie / Diem, Gabriel / Jäger, Michael / Zaderer, Viktoria / Lupoli, Gaia / Dächert, Christopher / Muenchhoff, Maximilian / Graf, Alexander / Blum, Helmut / Keppler, Oliver T / Lass-Flörl, Cornelia / Weiss, Günter / Wilflingseder, Doris / Posch, Wilfried

Antiviral research

2023 Volume 213, Page(s) 105581

Abstract: The identification of the SARS-CoV-2 Omicron variants BA.4/BA.5, BF.7 and BQ.1.1 immediately raised concerns regarding the efficacy of currently used monoclonal antibody therapies. Here we examined the activity of monoclonal antibody therapies and ... ...

Abstract	The identification of the SARS-CoV-2 Omicron variants BA.4/BA.5, BF.7 and BQ.1.1 immediately raised concerns regarding the efficacy of currently used monoclonal antibody therapies. Here we examined the activity of monoclonal antibody therapies and antiviral drugs against clinical specimens for SARS-CoV-2 Omicron BA.4/BA.5, BF.7 and BQ.1.1 employing an immunofluorescence neutralization assay. Further we explored treatment of BA.4/BA.5 infections with efficient antiviral drugs and monoclonal antibodies in a 3D model of primary human bronchial epithelial cells. We found that the antiviral drugs Molnupiravir, Nirmatrelvir and Remdesivir efficiently inhibit BA.4/BA.5, BF.7 and BQ.1.1 replication. In contrast, only the monoclonal antibody Cilgavimab exerted an inhibitory effect, while Tixagevimab, Regdanvimab and Sotrovimab lost their efficacy against BA.4/BA.5. We found that only the prophylactic treatment with Cilgavimab impacted on tissue inflammation by reducing intracellular complement component 3 (C3) activation following BA.4/BA.5 infection in primary human airway epithelial grown in air-liquid-interphase, which was not the case when using antiviral drugs or Cilgavimab after establishment of infection. Of note, all tested monoclonal antibodies had no neutralizing activity during infection by BF.7 and BQ.1.1 variants. Our results suggest that despite a marked reduction of viral replication, potent antiviral drugs fail to reduce tissue levels of inflammatory compounds such as C3, which can still result in tissue destruction.
MeSH term(s)	Humans ; COVID-19 ; SARS-CoV-2 ; Antibodies, Monoclonal ; Antibodies, Neutralizing/pharmacology ; Antiviral Agents/pharmacology ; Antibodies, Viral
Chemical Substances	Antibodies, Monoclonal ; Antibodies, Neutralizing ; Antiviral Agents ; Antibodies, Viral
Language	English
Publishing date	2023-03-23
Publishing country	Netherlands
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	306628-9
ISSN	1872-9096 ; 0166-3542
ISSN (online)	1872-9096
ISSN	0166-3542
DOI	10.1016/j.antiviral.2023.105581
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Article ; Online: Dexamethasone Creates a Suppressive Microenvironment and Promotes

Luvanda, Maureen K / Posch, Wilfried / Noureen, Asma / Lafon, Eliott / Zaderer, Viktoria / Lass-Flörl, Cornelia / Wilflingseder, Doris

Journal of fungi (Basel, Switzerland)

2021 Volume 7, Issue 3

Abstract: Lung immunity and susceptibility to infections is subject to interactions between the epithelial layer and immune cells residing in the pulmonary space. ...

Abstract	Lung immunity and susceptibility to infections is subject to interactions between the epithelial layer and immune cells residing in the pulmonary space.
Language	English
Publishing date	2021-03-18
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2784229-0
ISSN	2309-608X ; 2309-608X
ISSN (online)	2309-608X
ISSN	2309-608X
DOI	10.3390/jof7030221
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Article ; Online: Dexamethasone Promotes

Luvanda, Maureen K / Posch, Wilfried / Vosper, Jonathan / Zaderer, Viktoria / Noureen, Asma / Lass-Flörl, Cornelia / Wilflingseder, Doris

Journal of fungi (Basel, Switzerland)

2021 Volume 7, Issue 2

Abstract: Since long-term corticosteroid treatment is associated with emerging opportunistic fungal infections causing high morbidity and mortality in immune-suppressed individuals, here we characterized the impact of dexamethasone (Dex) treatment ... ...

Abstract	Since long-term corticosteroid treatment is associated with emerging opportunistic fungal infections causing high morbidity and mortality in immune-suppressed individuals, here we characterized the impact of dexamethasone (Dex) treatment on
Language	English
Publishing date	2021-01-20
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2784229-0
ISSN	2309-608X ; 2309-608X
ISSN (online)	2309-608X
ISSN	2309-608X
DOI	10.3390/jof7020070
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Article: P80 Natural Essence Exerts Efficient Anti-HIV-1- as Well as Adjuvant Effects in DCs.

Zaderer, Viktoria / Posch, Wilfried / Gstir, Ronald / Filipek, Przemyslaw A / Bonn, Günther K / Aramwit, Pornanong / Huber, Lukas A / Wilflingseder, Doris

Vaccines

2021 Volume 9, Issue 9

Abstract: 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 ...

Abstract	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.
Language	English
Publishing date	2021-08-31
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2703319-3
ISSN	2076-393X
ISSN	2076-393X
DOI	10.3390/vaccines9090976
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