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4-Octyl itaconate reduces influenza A replication by targeting the nuclear export protein CRM1.
Ribó-Molina, Pau; Weiss, Hauke J; Susma, Balasubramanian; van Nieuwkoop, Stefan; Persoons, Leentje; Zheng, Yunan; Ruzek, Melanie; Daelemans, Dirk; Fouchier, Ron A M; O'Neill, Luke A J; van den Hoogen, Bernadette G.
Afiliación
  • Ribó-Molina P; Department of Viroscience, Erasmus Medical Center , Rotterdam, the Netherlands.
  • Weiss HJ; School of Biochemistry and Immunology, Trinity Biomedical Sciences Institute, Trinity College Dublin , Dublin, Ireland.
  • Susma B; Department of Viroscience, Erasmus Medical Center , Rotterdam, the Netherlands.
  • van Nieuwkoop S; Department of Viroscience, Erasmus Medical Center , Rotterdam, the Netherlands.
  • Persoons L; Laboratory of Virology and Chemotherapy, KU Leuven Department of Microbiology, Immunology and Transplantation, Rega Institute, KU Leuven , Leuven, Belgium.
  • Zheng Y; AbbVie Bioresearch Center , Worcester, Massachusetts, USA.
  • Ruzek M; AbbVie Bioresearch Center , Worcester, Massachusetts, USA.
  • Daelemans D; Laboratory of Virology and Chemotherapy, KU Leuven Department of Microbiology, Immunology and Transplantation, Rega Institute, KU Leuven , Leuven, Belgium.
  • Fouchier RAM; Department of Viroscience, Erasmus Medical Center , Rotterdam, the Netherlands.
  • O'Neill LAJ; School of Biochemistry and Immunology, Trinity Biomedical Sciences Institute, Trinity College Dublin , Dublin, Ireland.
  • van den Hoogen BG; Department of Viroscience, Erasmus Medical Center , Rotterdam, the Netherlands.
J Virol ; 97(10): e0132523, 2023 10 31.
Article en En | MEDLINE | ID: mdl-37823646
IMPORTANCE: Itaconate derivates, as well as the naturally produced metabolite, have been proposed as antivirals against influenza virus. Here, the mechanism behind the antiviral effects of exogenous 4-octyl itaconate (4-OI), a derivative of itaconate, against the influenza A virus replication is demonstrated. The data indicate that 4-OI targets the cysteine at position 528 of the CRM1 protein, resulting in inhibition of the nuclear export of viral ribonucleoprotein complexes in a similar manner as previously described for other selective inhibitors of nuclear export. These results postulate a mechanism not observed before for this immuno-metabolite derivative. This knowledge is helpful for the development of derivatives of 4-OI as potential antiviral and anti-inflammatory therapeutics.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Antivirales / Succinatos / Replicación Viral / Gripe Humana / Proteína Exportina 1 Límite: Humans Idioma: En Revista: J Virol Año: 2023 Tipo del documento: Article País de afiliación: Países Bajos Pais de publicación: Estados Unidos
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Antivirales / Succinatos / Replicación Viral / Gripe Humana / Proteína Exportina 1 Límite: Humans Idioma: En Revista: J Virol Año: 2023 Tipo del documento: Article País de afiliación: Países Bajos Pais de publicación: Estados Unidos