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  1. Book ; Online ; Thesis: The deleterious role of neutrophil extracellular traps (NETs) in pneumococcal pneumonia and therapeutic treatment with adrenomedullin

    Teixeira Alves, Luiz Gustavo [Verfasser]

    2020  

    Author's details Luiz Gustavo Teixeira Alves
    Keywords Biowissenschaften, Biologie ; Life Science, Biology
    Subject code sg570
    Language English
    Publisher Freie Universität Berlin
    Publishing place Berlin
    Document type Book ; Online ; Thesis
    Database Digital theses on the web

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  2. Article ; Online: Protective role of the HSP90 inhibitor, STA-9090, in lungs of SARS-CoV-2-infected Syrian golden hamsters.

    Teixeira Alves, Luiz Gustavo / Baumgardt, Morris / Langner, Christine / Fischer, Mara / Maria Adler, Julia / Bushe, Judith / Firsching, Theresa Catharina / Mastrobuoni, Guido / Grobe, Jenny / Hoenzke, Katja / Kempa, Stefan / Gruber, Achim Dieter / Hocke, Andreas Christian / Trimpert, Jakob / Wyler, Emanuel / Landthaler, Markus

    BMJ open respiratory research

    2024  Volume 11, Issue 1

    Abstract: Introduction: The emergence of new SARS-CoV-2 variants, capable of escaping the humoral immunity acquired by the available vaccines, together with waning immunity and vaccine hesitancy, challenges the efficacy of the vaccination strategy in fighting ... ...

    Abstract Introduction: The emergence of new SARS-CoV-2 variants, capable of escaping the humoral immunity acquired by the available vaccines, together with waning immunity and vaccine hesitancy, challenges the efficacy of the vaccination strategy in fighting COVID-19. Improved therapeutic strategies are urgently needed to better intervene particularly in severe cases of the disease. They should aim at controlling the hyperinflammatory state generated on infection, reducing lung tissue pathology and inhibiting viral replication. Previous research has pointed to a possible role for the chaperone HSP90 in SARS-CoV-2 replication and COVID-19 pathogenesis. Pharmacological intervention through HSP90 inhibitors was shown to be beneficial in the treatment of inflammatory diseases, infections and reducing replication of diverse viruses.
    Methods: In this study, we investigated the effects of the potent HSP90 inhibitor Ganetespib (STA-9090) in vitro on alveolar epithelial cells and alveolar macrophages to characterise its effects on cell activation and viral replication. Additionally, the Syrian hamster animal model was used to evaluate its efficacy in controlling systemic inflammation and viral burden after infection.
    Results: In vitro, STA-9090 reduced viral replication on alveolar epithelial cells in a dose-dependent manner and lowered significantly the expression of proinflammatory genes, in both alveolar epithelial cells and alveolar macrophages. In vivo, although no reduction in viral load was observed, administration of STA-9090 led to an overall improvement of the clinical condition of infected animals, with reduced oedema formation and lung tissue pathology.
    Conclusion: Altogether, we show that HSP90 inhibition could serve as a potential treatment option for moderate and severe cases of COVID-19.
    MeSH term(s) Cricetinae ; Animals ; Humans ; Mesocricetus ; SARS-CoV-2 ; COVID-19/pathology ; Lung/pathology ; Triazoles
    Chemical Substances STA 9090 ; Triazoles
    Language English
    Publishing date 2024-02-29
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2736454-9
    ISSN 2052-4439 ; 2052-4439
    ISSN (online) 2052-4439
    ISSN 2052-4439
    DOI 10.1136/bmjresp-2023-001762
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: Neutrophil-Derived Extracellular Vesicles Activate Platelets after Pneumolysin Exposure.

    Letsiou, Eleftheria / Teixeira Alves, Luiz Gustavo / Felten, Matthias / Mitchell, Timothy J / Müller-Redetzky, Holger C / Dudek, Steven M / Witzenrath, Martin

    Cells

    2021  Volume 10, Issue 12

    Abstract: Pneumolysin (PLY) is a pore-forming toxin ... ...

    Abstract Pneumolysin (PLY) is a pore-forming toxin of
    MeSH term(s) Animals ; Bacterial Proteins/pharmacology ; Blood Platelets/drug effects ; Blood Platelets/metabolism ; Extracellular Traps/drug effects ; Extracellular Traps/metabolism ; Extracellular Vesicles/metabolism ; Humans ; Mice ; Neutrophil Activation/drug effects ; Neutrophils/metabolism ; Platelet Activation/drug effects ; Streptolysins/pharmacology
    Chemical Substances Bacterial Proteins ; Streptolysins ; plY protein, Streptococcus pneumoniae
    Language English
    Publishing date 2021-12-18
    Publishing country Switzerland
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2661518-6
    ISSN 2073-4409 ; 2073-4409
    ISSN (online) 2073-4409
    ISSN 2073-4409
    DOI 10.3390/cells10123581
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article: A single-dose MCMV-based vaccine elicits long-lasting immune protection in mice against distinct SARS-CoV-2 variants.

    Metzdorf, Kristin / Jacobsen, Henning / Kim, Yeonsu / Teixeira Alves, Luiz Gustavo / Kulkarni, Upasana / Eschke, Kathrin / Chaudhry, M Zeeshan / Hoffmann, Markus / Bertoglio, Federico / Ruschig, Maximilian / Hust, Michael / Cokarić Brdovčak, Maja / Materljan, Jelena / Šustić, Marko / Krmpotić, Astrid / Jonjić, Stipan / Widera, Marek / Ciesek, Sandra / Pöhlmann, Stefan /
    Landthaler, Markus / Čičin-Šain, Luka

    bioRxiv : the preprint server for biology

    2024  

    Abstract: Current vaccines against COVID-19 elicit immune responses that are overall strong but wane rapidly. As a consequence, the necessary booster shots have led to vaccine fatigue. Hence, vaccines that would provide lasting protection against COVID-19 are ... ...

    Abstract Current vaccines against COVID-19 elicit immune responses that are overall strong but wane rapidly. As a consequence, the necessary booster shots have led to vaccine fatigue. Hence, vaccines that would provide lasting protection against COVID-19 are needed, but are still unavailable. Cytomegaloviruses (CMV) elicit lasting and uniquely strong immune responses. Used as vaccine vectors, they may be attractive tools that obviate the need for boosters. Therefore, we tested the murine CMV (MCMV) as a vaccine vector against COVID-19 in relevant preclinical models of immunization and challenge. We have previously developed a recombinant murine CMV (MCMV) vaccine vector expressing the spike protein of the ancestral SARS-CoV-2 (MCMV
    Language English
    Publishing date 2024-02-15
    Publishing country United States
    Document type Preprint
    DOI 10.1101/2022.11.25.517953
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article ; Online: De Novo-Whole Genome Assembly of the Roborovski Dwarf Hamster (Phodopus roborovskii) Genome: An Animal Model for Severe/Critical COVID-19.

    Andreotti, Sandro / Altmüller, Janine / Quedenau, Claudia / Borodina, Tatiana / Nouailles, Geraldine / Teixeira Alves, Luiz Gustavo / Landthaler, Markus / Bieniara, Maximilian / Trimpert, Jakob / Wyler, Emanuel

    Genome biology and evolution

    2022  Volume 14, Issue 7

    Abstract: The Roborovski dwarf hamster Phodopus roborovskii belongs to the Phodopus genus, one of the seven within Cricetinae subfamily. Like other rodents such as mice, rats, or ferrets, hamsters can be important animal models for a range of diseases. Whereas the ...

    Abstract The Roborovski dwarf hamster Phodopus roborovskii belongs to the Phodopus genus, one of the seven within Cricetinae subfamily. Like other rodents such as mice, rats, or ferrets, hamsters can be important animal models for a range of diseases. Whereas the Syrian hamster from the genus Mesocricetus is now widely used as a model for mild-to-moderate coronavirus disease 2019, Roborovski dwarf hamster shows a severe-to-lethal course of disease upon infection with the novel human coronavirus severe acute respiratory syndrome coronavirus 2.
    MeSH term(s) Animals ; COVID-19/genetics ; Cricetinae ; Ferrets ; Humans ; Mice ; Models, Animal ; Phodopus ; Rats
    Language English
    Publishing date 2022-07-14
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2495328-3
    ISSN 1759-6653 ; 1759-6653
    ISSN (online) 1759-6653
    ISSN 1759-6653
    DOI 10.1093/gbe/evac100
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  6. Article ; Online: Single-cell-resolved interspecies comparison identifies a shared inflammatory axis and a dominant neutrophil-endothelial program in severe COVID-19

    Peidli, Stefan / Nouailles, Geraldine / Wyler, Emanuel / Adler, Julia M. / Kunder, Sandra / Voss, Anne / Kazmierski, Julia / Pott, Fabian / Pennitz, Peter / Postmus, Dylan / Teixeira Alves, Luiz Gustavo / Goffinet, Christine / Gruber, Achim D. / Bluethgen, Nils / Witzenrath, Martin / Trimpert, Jakob / Landthaler, Markus / Praktiknjo, Samantha D.

    bioRxiv

    Abstract: Key issues for research of COVID-19 pathogenesis are the lack of biopsies from patients and of samples at the onset of infection. To overcome these hurdles, hamsters were shown to be useful models for studying this disease. Here, we further leveraged the ...

    Abstract Key issues for research of COVID-19 pathogenesis are the lack of biopsies from patients and of samples at the onset of infection. To overcome these hurdles, hamsters were shown to be useful models for studying this disease. Here, we further leveraged the model to molecularly survey the disease progression from time-resolved single-cell RNA-sequencing data collected from healthy and SARS-CoV-2-infected Syrian and Roborovski hamster lungs. We compared our data to human COVID-19 studies, including BALF, nasal swab, and post-mortem lung tissue, and identified a shared axis of inflammation dominated by macrophages, neutrophils, and endothelial cells, which we show to be transient in Syrian and terminal in Roborovski hamsters. Our data suggest that, following SARS-CoV-2 infection, commitment to a type 1 or type 3-biased immunity determines moderate versus severe COVID-19 outcomes, respectively.
    Keywords covid19
    Language English
    Publishing date 2023-08-27
    Publisher Cold Spring Harbor Laboratory
    Document type Article ; Online
    DOI 10.1101/2023.08.25.551434
    Database COVID19

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  7. Article ; Online: Tissue protective role of Ganetespib in SARS-CoV-2-infected Syrian golden hamsters

    Teixeira Alves, Luiz Gustavo / Baumgardt, Morris / Hoppe, Judith / Firsching, Theresa C. / Adler, Julia M. / Mastrobuoni, Guido / Grobe, Jenny / Hönzke, Katja / Kempa, Stefan / Gruber, Achim D. / Hocke, Andreas C. / Trimpert, Jakob / Wyler, Emanuel / Landthaler, Markus

    bioRxiv

    Abstract: The emergence of new SARS-CoV-2 variants, capable of escaping the humoral immunity acquired by the available vaccines, together with waning immunity and vaccine hesitancy, challenges the efficacy of the vaccination strategy in fighting COVID-19. Improved ...

    Abstract The emergence of new SARS-CoV-2 variants, capable of escaping the humoral immunity acquired by the available vaccines, together with waning immunity and vaccine hesitancy, challenges the efficacy of the vaccination strategy in fighting COVID-19. Improved therapeutic strategies are therefore urgently needed to better intervene particularly in severe cases of the disease. They should aim at controlling the hyper-inflammatory state generated upon infection, at reducing lung tissue pathology and endothelial damages, along with viral replication. Previous research has pointed a possible role for the chaperone HSP90 in SARS-CoV-2 replication and COVID-19 pathogenesis. Pharmacological intervention through HSP90 inhibitors was shown to be beneficial in the treatment of inflammatory diseases, infections and reducing replication of diverse viruses. In this study, we analyzed the effects of the potent HSP90 inhibitor Ganetespib in vitro on alveolar epithelial cells and alveolar macrophages to characterize its effects on cell activation and viral replication. Additionally, to evaluate its efficacy in controlling systemic inflammation and the viral burden after infection in vivo, a Syrian hamster model was used. In vitro, Ganetespib reduced viral replication on AECs in a dose-dependent manner and lowered significantly the expression of pro-inflammatory genes, in both AECs and alveolar macrophages. In vivo, administration of Ganetespib led to an overall improvement of the clinical condition of infected animals, with decreased systemic inflammation, reduced edema formation and lung tissue pathology. Altogether, we show that Ganetespib could be a potential medicine to treat moderate and severe cases of COVID-19.
    Keywords covid19
    Language English
    Publishing date 2022-12-27
    Publisher Cold Spring Harbor Laboratory
    Document type Article ; Online
    DOI 10.1101/2022.12.27.521979
    Database COVID19

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  8. Article ; Online: Tissue protective role of Ganetespib in SARS-CoV-2-infected Syrian golden hamsters

    Teixeira Alves, Luiz Gustavo / Baumgardt, Morris / Hoppe, Judith / Firsching, Theresa C. / Adler, Julia M. / Mastrobuoni, Guido / Grobe, Jenny / Hoenzke, Katja / Kempa, Stefan / Gruber, Achim D. / Hocke, Andreas C. / Trimpert, Jakob / Wyler, Emanuel / Landthaler, Markus

    bioRxiv

    Abstract: The emergence of new SARS-CoV-2 variants, capable of escaping the humoral immunity acquired by the available vaccines, together with waning immunity and vaccine hesitancy, challenges the efficacy of the vaccination strategy in fighting COVID-19. Improved ...

    Abstract The emergence of new SARS-CoV-2 variants, capable of escaping the humoral immunity acquired by the available vaccines, together with waning immunity and vaccine hesitancy, challenges the efficacy of the vaccination strategy in fighting COVID-19. Improved therapeutic strategies are therefore urgently needed to better intervene particularly in severe cases of the disease. They should aim at controlling the hyper-inflammatory state generated upon infection, at reducing lung tissue pathology and endothelial damages, along with viral replication. Previous research has pointed a possible role for the chaperone HSP90 in SARS-CoV-2 replication and COVID-19 pathogenesis. Pharmacological intervention through HSP90 inhibitors was shown to be beneficial in the treatment of inflammatory diseases, infections and reducing replication of diverse viruses. In this study, we analyzed the effects of the potent HSP90 inhibitor Ganetespib in vitro on alveolar epithelial cells and alveolar macrophages to characterize its effects on cell activation and viral replication. Additionally, to evaluate its efficacy in controlling systemic inflammation and the viral burden after infection in vivo, a Syrian hamster model was used. In vitro, Ganetespib reduced viral replication on AECs in a dose-dependent manner and lowered significantly the expression of pro-inflammatory genes, in both AECs and alveolar macrophages. In vivo, administration of Ganetespib led to an overall improvement of the clinical condition of infected animals, with decreased systemic inflammation, reduced edema formation and lung tissue pathology. Altogether, we show that Ganetespib could be a potential medicine to treat moderate and severe cases of COVID-19.
    Keywords covid19
    Language English
    Publishing date 2022-12-27
    Publisher Cold Spring Harbor Laboratory
    Document type Article ; Online
    DOI 10.1101/2022.12.27.521979
    Database COVID19

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  9. Article ; Online: Ventilator-induced Lung Injury Is Modulated by the Circadian Clock.

    Felten, Matthias / Ferencik, Sebastian / Teixeira Alves, Luiz-Gustavo / Letsiou, Eleftheria / Lienau, Jasmin / Müller-Redetzky, Holger C / Langenhagen, Alina Katharina / Voß, Anne / Dietert, Kristina / Kershaw, Olivia / Gruber, Achim D / Michalick, Laura / Kuebler, Wolfgang M / Ananthasubramaniam, Bharath / Maier, Bert / Uhlenhaut, Henriette / Kramer, Achim / Witzenrath, Martin

    American journal of respiratory and critical care medicine

    2021  Volume 207, Issue 11, Page(s) 1464–1474

    Abstract: Rationale: ...

    Abstract Rationale:
    MeSH term(s) Mice ; Animals ; Circadian Clocks/genetics ; ARNTL Transcription Factors/genetics ; ARNTL Transcription Factors/metabolism ; Lung ; Ventilator-Induced Lung Injury/genetics ; Ventilator-Induced Lung Injury/metabolism ; Circadian Rhythm/genetics ; Mice, Inbred C57BL
    Chemical Substances ARNTL Transcription Factors
    Language English
    Publishing date 2021-05-31
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 1180953-x
    ISSN 1535-4970 ; 0003-0805 ; 1073-449X
    ISSN (online) 1535-4970
    ISSN 0003-0805 ; 1073-449X
    DOI 10.1164/rccm.202202-0320OC
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  10. Article ; Online: Loss of endothelial CFTR drives barrier failure and edema formation in lung infection and can be targeted by CFTR potentiation.

    Erfinanda, Lasti / Zou, Lin / Gutbier, Birgitt / Kneller, Laura / Weidenfeld, Sarah / Michalick, Laura / Lei, Disi / Reppe, Katrin / Teixeira Alves, Luiz Gustavo / Schneider, Bill / Zhang, Qi / Li, Caihong / Fatykhova, Diana / Schneider, Paul / Liedtke, Wolfgang / Sohara, Eisei / Mitchell, Timothy J / Gruber, Achim D / Hocke, Andreas /
    Hippenstiel, Stefan / Suttorp, Norbert / Olschewski, Andrea / Mall, Marcus A / Witzenrath, Martin / Kuebler, Wolfgang M

    Science translational medicine

    2022  Volume 14, Issue 674, Page(s) eabg8577

    Abstract: Pneumonia is the most common cause of the acute respiratory distress syndrome (ARDS). Here, we identified loss of endothelial cystic fibrosis transmembrane conductance regulator (CFTR) as an important pathomechanism leading to lung barrier failure in ... ...

    Abstract Pneumonia is the most common cause of the acute respiratory distress syndrome (ARDS). Here, we identified loss of endothelial cystic fibrosis transmembrane conductance regulator (CFTR) as an important pathomechanism leading to lung barrier failure in pneumonia-induced ARDS. CFTR was down-regulated after
    MeSH term(s) Humans ; Mice ; Animals ; Chlorides ; Calcium ; Pneumonia ; Lung ; Cystic Fibrosis Transmembrane Conductance Regulator ; TRPV Cation Channels
    Chemical Substances Chlorides ; Calcium (SY7Q814VUP) ; CFTR protein, human ; Cystic Fibrosis Transmembrane Conductance Regulator (126880-72-6) ; Trpv4 protein, mouse ; TRPV Cation Channels
    Language English
    Publishing date 2022-12-07
    Publishing country United States
    Document type Journal Article
    ZDB-ID 2518854-9
    ISSN 1946-6242 ; 1946-6234
    ISSN (online) 1946-6242
    ISSN 1946-6234
    DOI 10.1126/scitranslmed.abg8577
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