PuSH - Publikationsserver des Helmholtz Zentrums München

Berthold, E. ; Ma-Lauer, Y.* ; Chakraborty, A. ; von Brunn, B.* ; Hilgendorff, A. ; Hatz, R.A.* ; Behr, J.* ; Hausch, F.* ; Staab-Weijnitz, C.A. ; von Brunn, A. *

Effects of immunophilin inhibitors and non-immunosuppressive analogs on coronavirus replication in human infection models.

Front. Cell. Infect. Microbiol. 12:958634 (2022)
Verlagsversion Forschungsdaten DOI PMC
Open Access Gold
Creative Commons Lizenzvertrag
Rationale: Human coronaviruses (HCoVs) seriously affect human health by causing respiratory diseases ranging from common colds to severe acute respiratory diseases. Immunophilins, including peptidyl-prolyl isomerases of the FK506-binding protein (FKBP) and the cyclophilin family, are promising targets for pharmaceutical inhibition of coronavirus replication, but cell-type specific effects have not been elucidated. FKBPs and cyclophilins bind the immunosuppressive drugs FK506 and cyclosporine A (CsA), respectively. Methods: Primary human bronchial epithelial cells (phBECs) were treated with CsA, Alisporivir (ALV), FK506, and FK506-derived non-immunosuppressive analogs and infected with HCoV-229E. RNA and protein were assessed by RT-qPCR and immunoblot analysis. Treatment with the same compounds was performed in hepatoma cells (Huh-7.5) infected with HCoV-229E expressing Renilla luciferase (HCoV-229E-RLuc) and the kidney cell line HEK293 transfected with a SARS-CoV-1 replicon expressing Renilla luciferase (SARS-CoV-1-RLuc), followed by quantification of luminescence as a measure of viral replication. Results: Both CsA and ALV robustly inhibited viral replication in all models; both compounds decreased HCoV-229E RNA in phBECs and reduced luminescence in HCoV-229E-RLuc-infected Huh7.5 and SARS-CoV-1-RLuc replicon-transfected HEK293. In contrast, FK506 showed inconsistent and less pronounced effects in phBECs while strongly affecting coronavirus replication in Huh-7.5 and HEK293. Two non-immunosuppressive FK506 analogs had no antiviral effect in any infection model. Conclusion: The immunophilin inhibitors CsA and ALV display robust anti-coronaviral properties in multiple infection models, including phBECs, reflecting a primary site of HCoV infection. In contrast, FK506 displayed cell-type specific effects, strongly affecting CoV replication in Huh7.5 and HEK293, but inconsistently and less pronounced in phBECs.
Altmetric
Weitere Metriken?
[➜Einloggen]
Zusatzinfos bearbeiten [➜Einloggen]
Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Korrespondenzautor
Schlagwörter Cyclosporin A ; Fk506 ; Hcov-229e ; Non-immunosuppressive Analogs ; Phbecs ; Tacrolimus
ISSN (print) / ISBN 2235-2988
e-ISSN 2235-2988
Zeitschrift Frontiers in Cellular and Infection Microbiology
Quellenangaben Band: 12, Heft: , Seiten: , Artikelnummer: 958634 Supplement: ,
Verlag Frontiers
Verlagsort Lausanne
Nichtpatentliteratur Publikationen
Begutachtungsstatus Peer reviewed
Institut(e) Lung Health and Immunity (LHI)
Förderungen Deutsches Zentrum für Lungenforschung
Helmholtz Association
Bundesinstitut für Risikobewertung
Deutsche Forschungsgemeinschaft
Deutsches Zentrum für Infektionsforschung
LOEWE Exploration