Berthold, Emilia J. ; Ma-Lauer, Yue ; Chakraborty, Ashesh ; Brunn, Brigitte von ; Hilgendorff, Anne ; Hatz, Rudolf ; Behr, Jürgen ; Hausch, Felix ; Staab-Weijnitz, Claudia A. ; Brunn, Albrecht von (2022)
Effects of immunophilin inhibitors and non-immunosuppressive analogs on coronavirus replication in human infection models.
In: Frontiers in Cellular and Infection Microbiology, 2022, 12
doi: 10.26083/tuprints-00022480
Artikel, Zweitveröffentlichung, Verlagsversion
 | Es ist eine neuere Version dieses Eintrags verfügbar. |
Kurzbeschreibung (Abstract)
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.
| Typ des Eintrags: | Artikel |
|---|---|
| Erschienen: | 2022 |
| Autor(en): | Berthold, Emilia J. ; Ma-Lauer, Yue ; Chakraborty, Ashesh ; Brunn, Brigitte von ; Hilgendorff, Anne ; Hatz, Rudolf ; Behr, Jürgen ; Hausch, Felix ; Staab-Weijnitz, Claudia A. ; Brunn, Albrecht von |
| Art des Eintrags: | Zweitveröffentlichung |
| Titel: | Effects of immunophilin inhibitors and non-immunosuppressive analogs on coronavirus replication in human infection models |
| Sprache: | Englisch |
| Publikationsjahr: | 2022 |
| Ort: | Darmstadt |
| Publikationsdatum der Erstveröffentlichung: | 2022 |
| Verlag: | Frontiers Media S.A. |
| Titel der Zeitschrift, Zeitung oder Schriftenreihe: | Frontiers in Cellular and Infection Microbiology |
| Jahrgang/Volume einer Zeitschrift: | 12 |
| Kollation: | 12 Seiten |
| DOI: | 10.26083/tuprints-00022480 |
| URL / URN: | https://tuprints.ulb.tu-darmstadt.de/22480 |
| Zugehörige Links: | |
| Herkunft: | Zweitveröffentlichung DeepGreen |
| Kurzbeschreibung (Abstract): | 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. |
| Freie Schlagworte: | HCoV-229E, Cyclosporin A, FK506, non-immunosuppressive analogs, pHBECs, tacrolimus |
| Status: | Verlagsversion |
| URN: | urn:nbn:de:tuda-tuprints-224804 |
| Sachgruppe der Dewey Dezimalklassifikatin (DDC): | 500 Naturwissenschaften und Mathematik > 540 Chemie 500 Naturwissenschaften und Mathematik > 570 Biowissenschaften, Biologie |
| Fachbereich(e)/-gebiet(e): | 07 Fachbereich Chemie 07 Fachbereich Chemie > Clemens-Schöpf-Institut > Fachgebiet Biochemie 07 Fachbereich Chemie > Clemens-Schöpf-Institut |
| Hinterlegungsdatum: | 24 Okt 2022 13:15 |
| Letzte Änderung: | 02 Aug 2024 12:43 |
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| Suche nach Titel in: | TUfind oder in Google |
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