Influenza H5Nx viruses are susceptible to MEK1/2 inhibition by zapnometinib
Highly pathogenic avian influenza A viruses (HPAIV) pose a significant threat to both animal and human health. These viruses have the potential to cause severe respiratory and systemic infections in birds and several mammalian species. The recent global outbreak of the H5N1 clade 2.3.4.4b spread in...
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| Format: | Article |
| Language: | English |
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Taylor & Francis Group
2025-12-01
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| Series: | Emerging Microbes and Infections |
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| Online Access: | https://www.tandfonline.com/doi/10.1080/22221751.2025.2471022 |
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| author | André Schreiber Nicole Oberberg Benjamin Ambrosy Franziska Rodner Sriram Kumar Duygu Merve Caliskan Linda Brunotte Martin Beer Stephan Ludwig |
| author_facet | André Schreiber Nicole Oberberg Benjamin Ambrosy Franziska Rodner Sriram Kumar Duygu Merve Caliskan Linda Brunotte Martin Beer Stephan Ludwig |
| author_sort | André Schreiber |
| collection | DOAJ |
| description | Highly pathogenic avian influenza A viruses (HPAIV) pose a significant threat to both animal and human health. These viruses have the potential to cause severe respiratory and systemic infections in birds and several mammalian species. The recent global outbreak of the H5N1 clade 2.3.4.4b spread in wild and domestic birds is now considered to be a panzoonosis. Spillover events in dairy cattle farms in the U.S. have highlighted the urgent need for effective antiviral therapies, especially in view of human infections. This study investigates the selective MEK1/2 inhibitor zapnometinib (ZMN) as a potential antiviral agent against HPAIVs. Our in vitro experiments demonstrate that ZMN significantly impairs viral replication across multiple HPAIV strains, including H5N1 clade 2.3.4.4b in cell lines and primary bronchial epithelial cells. The mechanism of action is based on the nuclear retention of newly produced viral ribonucleoprotein complexes (vRNP), when the MEK/ERK/RSK1 kinase cascade is inhibited. We furthermore could show, that ZMN not only acts antiviral in a standalone treatment but has synergistic potential when used in combination with direct-acting antivirals like oseltamivir or baloxavir. Therefore, ZMN treatment offers a promising strategy for future antiviral development. |
| format | Article |
| id | doaj-art-de01396cc1924722a5ae496fde63c488 |
| institution | OA Journals |
| issn | 2222-1751 |
| language | English |
| publishDate | 2025-12-01 |
| publisher | Taylor & Francis Group |
| record_format | Article |
| series | Emerging Microbes and Infections |
| spelling | doaj-art-de01396cc1924722a5ae496fde63c4882025-08-20T02:30:10ZengTaylor & Francis GroupEmerging Microbes and Infections2222-17512025-12-0114110.1080/22221751.2025.2471022Influenza H5Nx viruses are susceptible to MEK1/2 inhibition by zapnometinibAndré Schreiber0Nicole Oberberg1Benjamin Ambrosy2Franziska Rodner3Sriram Kumar4Duygu Merve Caliskan5Linda Brunotte6Martin Beer7Stephan Ludwig8Institute of Virology Muenster, University of Muenster, Muenster, GermanyInstitute of Virology Muenster, University of Muenster, Muenster, GermanyInstitute of Virology Muenster, University of Muenster, Muenster, GermanyInstitute of Virology Muenster, University of Muenster, Muenster, GermanyInstitute of Virology Muenster, University of Muenster, Muenster, GermanyInstitute of Virology Muenster, University of Muenster, Muenster, GermanyInstitute of Virology Muenster, University of Muenster, Muenster, GermanyInstitute of Diagnostic Virology, Friedrich-Loeffler-Institut, Greifswald-Insel Riems, GermanyInstitute of Virology Muenster, University of Muenster, Muenster, GermanyHighly pathogenic avian influenza A viruses (HPAIV) pose a significant threat to both animal and human health. These viruses have the potential to cause severe respiratory and systemic infections in birds and several mammalian species. The recent global outbreak of the H5N1 clade 2.3.4.4b spread in wild and domestic birds is now considered to be a panzoonosis. Spillover events in dairy cattle farms in the U.S. have highlighted the urgent need for effective antiviral therapies, especially in view of human infections. This study investigates the selective MEK1/2 inhibitor zapnometinib (ZMN) as a potential antiviral agent against HPAIVs. Our in vitro experiments demonstrate that ZMN significantly impairs viral replication across multiple HPAIV strains, including H5N1 clade 2.3.4.4b in cell lines and primary bronchial epithelial cells. The mechanism of action is based on the nuclear retention of newly produced viral ribonucleoprotein complexes (vRNP), when the MEK/ERK/RSK1 kinase cascade is inhibited. We furthermore could show, that ZMN not only acts antiviral in a standalone treatment but has synergistic potential when used in combination with direct-acting antivirals like oseltamivir or baloxavir. Therefore, ZMN treatment offers a promising strategy for future antiviral development.https://www.tandfonline.com/doi/10.1080/22221751.2025.2471022HPAIVantiviral drug treatmentRaf/MEK/ERK signalling pathwayMEK1/2 inhibitionZapnometinib |
| spellingShingle | André Schreiber Nicole Oberberg Benjamin Ambrosy Franziska Rodner Sriram Kumar Duygu Merve Caliskan Linda Brunotte Martin Beer Stephan Ludwig Influenza H5Nx viruses are susceptible to MEK1/2 inhibition by zapnometinib Emerging Microbes and Infections HPAIV antiviral drug treatment Raf/MEK/ERK signalling pathway MEK1/2 inhibition Zapnometinib |
| title | Influenza H5Nx viruses are susceptible to MEK1/2 inhibition by zapnometinib |
| title_full | Influenza H5Nx viruses are susceptible to MEK1/2 inhibition by zapnometinib |
| title_fullStr | Influenza H5Nx viruses are susceptible to MEK1/2 inhibition by zapnometinib |
| title_full_unstemmed | Influenza H5Nx viruses are susceptible to MEK1/2 inhibition by zapnometinib |
| title_short | Influenza H5Nx viruses are susceptible to MEK1/2 inhibition by zapnometinib |
| title_sort | influenza h5nx viruses are susceptible to mek1 2 inhibition by zapnometinib |
| topic | HPAIV antiviral drug treatment Raf/MEK/ERK signalling pathway MEK1/2 inhibition Zapnometinib |
| url | https://www.tandfonline.com/doi/10.1080/22221751.2025.2471022 |
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