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Teixeira Alves, L.G.* ; Baumgardt, M.* ; Langner, C.* ; Fischer, M.* ; Maria Adler, J.* ; Bushe, J. ; Firsching, T.C.* ; Mastrobuoni, G.* ; Grobe, J.* ; Hoenzke, K.* ; Kempa, S.* ; Gruber, A.D.* ; Hocke, A.C.* ; Trimpert, J.* ; Wyler, E.* ; Landthaler, M.*

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

BMJ Open Respir. Res. 11:e001762 (2024)
Postprint DOI PMC
Open Access Gold
Creative Commons Lizenzvertrag
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.
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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Schlagwörter Covid-19 ; Inflammation ; Pneumonia ; Respiratory Infection; Covid-19; Replication; Cells
Sprache englisch
Veröffentlichungsjahr 2024
HGF-Berichtsjahr 2024
ISSN (print) / ISBN 2052-4439
e-ISSN 2052-4439
Zeitschrift BMJ Open Respiratory Research
Quellenangaben Band: 11, Heft: 1, Seiten: , Artikelnummer: e001762 Supplement: ,
Verlag BMJ Publishing Group
Verlagsort London
Institut(e) Research Unit Analytical Pathology (AAP)
POF Topic(s) 30205 - Bioengineering and Digital Health
Forschungsfeld(er) Enabling and Novel Technologies
PSP-Element(e) G-500390-001
Förderungen DFG
Einstein Foundation EC3R
BMBF
BMBF (RAPID)
Helmholtz Association Initiative and Networking Fund
Project 'Virological and immunological determinants of COVID- 19 pathogenesis-lessons to get prepared for future pandemics
BIH/MDC Genomics Technology platform in Berlin for the sequencing
DOI 10.1136/bmjresp-2023-001762
WOS ID 001179393600004
PubMed ID 38423952
Erfassungsdatum 2024-04-29
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