The Combination of GS-441524 (Remdesivir) and Ribavirin Results in a Potent Antiviral Effect Against Human Parainfluenza Virus 3 Infection in Human Airway Epithelial Cell Cultures and in a Mouse Infection Model
Human parainfluenza virus type 3 (HPIV-3) can cause severe respiratory diseases, particularly in young children, the elderly and immunocompromised. There are no approved antiviral drugs against this virus. We report that the combination of ribavirin with either remdesivir or its parent nucleoside GS...
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| author | Yuxia Lin Birgit Weynand Xin Zhang Manon Laporte Dirk Jochmans Johan Neyts |
| author_facet | Yuxia Lin Birgit Weynand Xin Zhang Manon Laporte Dirk Jochmans Johan Neyts |
| author_sort | Yuxia Lin |
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| description | Human parainfluenza virus type 3 (HPIV-3) can cause severe respiratory diseases, particularly in young children, the elderly and immunocompromised. There are no approved antiviral drugs against this virus. We report that the combination of ribavirin with either remdesivir or its parent nucleoside GS-441524 results in a pronounced antiviral effect against HPIV-3 in LLC-MK2 cells and in human airway epithelial cells grown at the air–liquid interface. In AG129 mice intranasally inoculated with HPIV-3, the combined treatment with ribavirin and GS-441524 decreased infectious viral lung titers by >2.5 log<sub>10</sub> to undetectable levels in 4 out of 11 mice and by 1.6 log<sub>10</sub> in the remaining 7 mice as compared with the vehicle. The lungs of all mice that received the combined treatment appeared histologically normal or virtually normal, whereas 8 of 11 vehicle-treated mice presented with bronchopneumonia. By contrast, ribavirin alone did not result in a reduction in infectious viral lung titers; GS-441524 alone reduced infectious viral lung titers by 1.2 log<sub>10</sub>. Moreover, several mice in the single-treatment groups exhibited severe lung pathology. These findings may warrant exploring this combination in patients with severe HPIV-3 infections and possibly also against infections with other viruses that are susceptible in vitro to these two drugs. |
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| spelling | doaj-art-5d1ce5209c054860b370d439194ae3102025-08-20T02:04:05ZengMDPI AGViruses1999-49152025-01-0117217210.3390/v17020172The Combination of GS-441524 (Remdesivir) and Ribavirin Results in a Potent Antiviral Effect Against Human Parainfluenza Virus 3 Infection in Human Airway Epithelial Cell Cultures and in a Mouse Infection ModelYuxia Lin0Birgit Weynand1Xin Zhang2Manon Laporte3Dirk Jochmans4Johan Neyts5KU Leuven Department of Microbiology, Immunology and Transplantation, Rega Institute for Medical Research, Virology, Antiviral Drug & Vaccine Research Group, B-3000 Leuven, BelgiumKU Leuven Department of Imaging and Pathology, Division of Translational Cell and Tissue Research, B-3000 Leuven, BelgiumKU Leuven Department of Microbiology, Immunology and Transplantation, Rega Institute for Medical Research, Virology, Antiviral Drug & Vaccine Research Group, B-3000 Leuven, BelgiumKU Leuven Department of Microbiology, Immunology and Transplantation, Rega Institute for Medical Research, Virology, Antiviral Drug & Vaccine Research Group, B-3000 Leuven, BelgiumKU Leuven Department of Microbiology, Immunology and Transplantation, Rega Institute for Medical Research, Virology, Antiviral Drug & Vaccine Research Group, B-3000 Leuven, BelgiumKU Leuven Department of Microbiology, Immunology and Transplantation, Rega Institute for Medical Research, Virology, Antiviral Drug & Vaccine Research Group, B-3000 Leuven, BelgiumHuman parainfluenza virus type 3 (HPIV-3) can cause severe respiratory diseases, particularly in young children, the elderly and immunocompromised. There are no approved antiviral drugs against this virus. We report that the combination of ribavirin with either remdesivir or its parent nucleoside GS-441524 results in a pronounced antiviral effect against HPIV-3 in LLC-MK2 cells and in human airway epithelial cells grown at the air–liquid interface. In AG129 mice intranasally inoculated with HPIV-3, the combined treatment with ribavirin and GS-441524 decreased infectious viral lung titers by >2.5 log<sub>10</sub> to undetectable levels in 4 out of 11 mice and by 1.6 log<sub>10</sub> in the remaining 7 mice as compared with the vehicle. The lungs of all mice that received the combined treatment appeared histologically normal or virtually normal, whereas 8 of 11 vehicle-treated mice presented with bronchopneumonia. By contrast, ribavirin alone did not result in a reduction in infectious viral lung titers; GS-441524 alone reduced infectious viral lung titers by 1.2 log<sub>10</sub>. Moreover, several mice in the single-treatment groups exhibited severe lung pathology. These findings may warrant exploring this combination in patients with severe HPIV-3 infections and possibly also against infections with other viruses that are susceptible in vitro to these two drugs.https://www.mdpi.com/1999-4915/17/2/172parainfluenza viruseshuman respirovirus 3remdesivirobeldesivirribavirinAG129 mice |
| spellingShingle | Yuxia Lin Birgit Weynand Xin Zhang Manon Laporte Dirk Jochmans Johan Neyts The Combination of GS-441524 (Remdesivir) and Ribavirin Results in a Potent Antiviral Effect Against Human Parainfluenza Virus 3 Infection in Human Airway Epithelial Cell Cultures and in a Mouse Infection Model Viruses parainfluenza viruses human respirovirus 3 remdesivir obeldesivir ribavirin AG129 mice |
| title | The Combination of GS-441524 (Remdesivir) and Ribavirin Results in a Potent Antiviral Effect Against Human Parainfluenza Virus 3 Infection in Human Airway Epithelial Cell Cultures and in a Mouse Infection Model |
| title_full | The Combination of GS-441524 (Remdesivir) and Ribavirin Results in a Potent Antiviral Effect Against Human Parainfluenza Virus 3 Infection in Human Airway Epithelial Cell Cultures and in a Mouse Infection Model |
| title_fullStr | The Combination of GS-441524 (Remdesivir) and Ribavirin Results in a Potent Antiviral Effect Against Human Parainfluenza Virus 3 Infection in Human Airway Epithelial Cell Cultures and in a Mouse Infection Model |
| title_full_unstemmed | The Combination of GS-441524 (Remdesivir) and Ribavirin Results in a Potent Antiviral Effect Against Human Parainfluenza Virus 3 Infection in Human Airway Epithelial Cell Cultures and in a Mouse Infection Model |
| title_short | The Combination of GS-441524 (Remdesivir) and Ribavirin Results in a Potent Antiviral Effect Against Human Parainfluenza Virus 3 Infection in Human Airway Epithelial Cell Cultures and in a Mouse Infection Model |
| title_sort | combination of gs 441524 remdesivir and ribavirin results in a potent antiviral effect against human parainfluenza virus 3 infection in human airway epithelial cell cultures and in a mouse infection model |
| topic | parainfluenza viruses human respirovirus 3 remdesivir obeldesivir ribavirin AG129 mice |
| url | https://www.mdpi.com/1999-4915/17/2/172 |
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