Promising Inhibitor of Flavivirus: Evaluating the Antiviral Activity of Nordihydroguaiaretic Acid against West Nile Virus Replication
- Autores
- Ghietto, Lucía María; Lingua, Giuliana; Gil, Pedro Ignacio; Aguilar, Juan Javier; Gomez, Tomás Isaac; Marioni, Juliana; Núñez Montoya, Susana Carolina; Konigheim, Brenda Salome; Martinez, Florencia
- Año de publicación
- 2025
- Idioma
- inglés
- Tipo de recurso
- conjunto de datos
- Estado
- Descripción
- Mosquito-borne Arboviruses, including Alphaviruses and Flaviviruses, are responsible for millions of human infections worldwide. The absence of specific antivirals for arbovirus infections underscores the urgent need for novel research to develop effective treatments. Natural products have emerged as promising candidates. Nordihydroguaiaretic acid (NDGA), a natural lignan predominantly found in Larrea spp., has shown antiviral activity against several viruses, including Dengue. This study aimed to investigate the antiviral potential of NDGA against West Nile virus (WNV), assessing its mechanism of action and cellular interactions. Using plaque-forming unit reduction and immunofluorescence assays in LLC-MK2 cells, we determine the reduction in viability of WNV viral particles at different times post-infection. The potential involvement of the sterol regulatory element-binding proteins (SREBP) and 5-lipoxygenase pathways in WNV infection was evaluated. Additionally, we analyzed the cytoskeleton integrity in treated cells. NDGA, had the greatest inhibitory effect on WNV replication when added 1 and 2 h post-viral internalization (PI), losing activity when added after 3 h PI, thus suggesting it targets early viral infection events. The SREBP pathway seems to be involved in the inhibition of WNV by NDGA, likely due to its lipogenic activity. Furthermore, the antiviral activity of NDGA could be related to its ability to modify the cytoskeleton of LLC-MK2 cells. These findings highlight NDGA potential as a therapeutic candidate against WNV and other flaviviruses. Plant metabolites are among the leading therapeutic resources globally. Further research is necessary to comprehensively assess the therapeutic promise of NDGA.
Fil: Ghietto, Lucía María. Universidad Nacional de Córdoba. Facultad de Medicina. Instituto de Virología Dr. J. M. Vanella; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba; Argentina
Fil: Lingua, Giuliana. Universidad Nacional de Córdoba. Facultad de Medicina. Instituto de Virología Dr. J. M. Vanella; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba; Argentina
Fil: Gil, Pedro Ignacio. Universidad Nacional de Córdoba. Facultad de Medicina. Instituto de Virología Dr. J. M. Vanella; Argentina
Fil: Aguilar, Juan Javier. Universidad Nacional de Córdoba. Facultad de Medicina. Instituto de Virología Dr. J. M. Vanella; Argentina
Fil: Gomez, Tomás Isaac. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Unidad de Investigación y Desarrollo en Tecnología Farmacéutica. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Unidad de Investigación y Desarrollo en Tecnología Farmacéutica; Argentina. Universidad Nacional de Córdoba. Facultad de Medicina. Instituto de Virología Dr. J. M. Vanella; Argentina
Fil: Marioni, Juliana. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Unidad de Investigación y Desarrollo en Tecnología Farmacéutica. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Unidad de Investigación y Desarrollo en Tecnología Farmacéutica; Argentina
Fil: Núñez Montoya, Susana Carolina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Unidad de Investigación y Desarrollo en Tecnología Farmacéutica. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Unidad de Investigación y Desarrollo en Tecnología Farmacéutica; Argentina
Fil: Konigheim, Brenda Salome. Universidad Nacional de Córdoba. Facultad de Medicina. Instituto de Virología Dr. J. M. Vanella; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba; Argentina
Fil: Martinez, Florencia. Universidad Nacional de Córdoba. Facultad de Medicina. Instituto de Virología Dr. J. M. Vanella; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba; Argentina - Nivel de accesibilidad
- acceso abierto
- Condiciones de uso
- https://creativecommons.org/licenses/by-nc-nd/2.5/ar/
- Repositorio
.jpg)
- Institución
- Consejo Nacional de Investigaciones Científicas y Técnicas
- OAI Identificador
- oai:ri.conicet.gov.ar:11336/258661
Ver los metadatos del registro completo
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Promising Inhibitor of Flavivirus: Evaluating the Antiviral Activity of Nordihydroguaiaretic Acid against West Nile Virus ReplicationGhietto, Lucía MaríaLingua, GiulianaGil, Pedro IgnacioAguilar, Juan JavierGomez, Tomás IsaacMarioni, JulianaNúñez Montoya, Susana CarolinaKonigheim, Brenda SalomeMartinez, Florenciahttps://purl.org/becyt/ford/1.6https://purl.org/becyt/ford/1Mosquito-borne Arboviruses, including Alphaviruses and Flaviviruses, are responsible for millions of human infections worldwide. The absence of specific antivirals for arbovirus infections underscores the urgent need for novel research to develop effective treatments. Natural products have emerged as promising candidates. Nordihydroguaiaretic acid (NDGA), a natural lignan predominantly found in Larrea spp., has shown antiviral activity against several viruses, including Dengue. This study aimed to investigate the antiviral potential of NDGA against West Nile virus (WNV), assessing its mechanism of action and cellular interactions. Using plaque-forming unit reduction and immunofluorescence assays in LLC-MK2 cells, we determine the reduction in viability of WNV viral particles at different times post-infection. The potential involvement of the sterol regulatory element-binding proteins (SREBP) and 5-lipoxygenase pathways in WNV infection was evaluated. Additionally, we analyzed the cytoskeleton integrity in treated cells. NDGA, had the greatest inhibitory effect on WNV replication when added 1 and 2 h post-viral internalization (PI), losing activity when added after 3 h PI, thus suggesting it targets early viral infection events. The SREBP pathway seems to be involved in the inhibition of WNV by NDGA, likely due to its lipogenic activity. Furthermore, the antiviral activity of NDGA could be related to its ability to modify the cytoskeleton of LLC-MK2 cells. These findings highlight NDGA potential as a therapeutic candidate against WNV and other flaviviruses. Plant metabolites are among the leading therapeutic resources globally. Further research is necessary to comprehensively assess the therapeutic promise of NDGA.Fil: Ghietto, Lucía María. Universidad Nacional de Córdoba. Facultad de Medicina. Instituto de Virología Dr. J. M. Vanella; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba; ArgentinaFil: Lingua, Giuliana. Universidad Nacional de Córdoba. Facultad de Medicina. Instituto de Virología Dr. J. M. Vanella; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba; ArgentinaFil: Gil, Pedro Ignacio. Universidad Nacional de Córdoba. Facultad de Medicina. Instituto de Virología Dr. J. M. Vanella; ArgentinaFil: Aguilar, Juan Javier. Universidad Nacional de Córdoba. Facultad de Medicina. Instituto de Virología Dr. J. M. Vanella; ArgentinaFil: Gomez, Tomás Isaac. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Unidad de Investigación y Desarrollo en Tecnología Farmacéutica. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Unidad de Investigación y Desarrollo en Tecnología Farmacéutica; Argentina. Universidad Nacional de Córdoba. Facultad de Medicina. Instituto de Virología Dr. J. M. Vanella; ArgentinaFil: Marioni, Juliana. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Unidad de Investigación y Desarrollo en Tecnología Farmacéutica. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Unidad de Investigación y Desarrollo en Tecnología Farmacéutica; ArgentinaFil: Núñez Montoya, Susana Carolina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Unidad de Investigación y Desarrollo en Tecnología Farmacéutica. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Unidad de Investigación y Desarrollo en Tecnología Farmacéutica; ArgentinaFil: Konigheim, Brenda Salome. Universidad Nacional de Córdoba. Facultad de Medicina. Instituto de Virología Dr. J. M. Vanella; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba; ArgentinaFil: Martinez, Florencia. Universidad Nacional de Córdoba. Facultad de Medicina. Instituto de Virología Dr. J. M. Vanella; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. 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| dc.title.none.fl_str_mv |
Promising Inhibitor of Flavivirus: Evaluating the Antiviral Activity of Nordihydroguaiaretic Acid against West Nile Virus Replication |
| title |
Promising Inhibitor of Flavivirus: Evaluating the Antiviral Activity of Nordihydroguaiaretic Acid against West Nile Virus Replication |
| spellingShingle |
Promising Inhibitor of Flavivirus: Evaluating the Antiviral Activity of Nordihydroguaiaretic Acid against West Nile Virus Replication Ghietto, Lucía María |
| title_short |
Promising Inhibitor of Flavivirus: Evaluating the Antiviral Activity of Nordihydroguaiaretic Acid against West Nile Virus Replication |
| title_full |
Promising Inhibitor of Flavivirus: Evaluating the Antiviral Activity of Nordihydroguaiaretic Acid against West Nile Virus Replication |
| title_fullStr |
Promising Inhibitor of Flavivirus: Evaluating the Antiviral Activity of Nordihydroguaiaretic Acid against West Nile Virus Replication |
| title_full_unstemmed |
Promising Inhibitor of Flavivirus: Evaluating the Antiviral Activity of Nordihydroguaiaretic Acid against West Nile Virus Replication |
| title_sort |
Promising Inhibitor of Flavivirus: Evaluating the Antiviral Activity of Nordihydroguaiaretic Acid against West Nile Virus Replication |
| dc.creator.none.fl_str_mv |
Ghietto, Lucía María Lingua, Giuliana Gil, Pedro Ignacio Aguilar, Juan Javier Gomez, Tomás Isaac Marioni, Juliana Núñez Montoya, Susana Carolina Konigheim, Brenda Salome Martinez, Florencia |
| author |
Ghietto, Lucía María |
| author_facet |
Ghietto, Lucía María Lingua, Giuliana Gil, Pedro Ignacio Aguilar, Juan Javier Gomez, Tomás Isaac Marioni, Juliana Núñez Montoya, Susana Carolina Konigheim, Brenda Salome Martinez, Florencia |
| author_role |
author |
| author2 |
Lingua, Giuliana Gil, Pedro Ignacio Aguilar, Juan Javier Gomez, Tomás Isaac Marioni, Juliana Núñez Montoya, Susana Carolina Konigheim, Brenda Salome Martinez, Florencia |
| author2_role |
author author author author author author author author |
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https://purl.org/becyt/ford/1.6 https://purl.org/becyt/ford/1 |
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Mosquito-borne Arboviruses, including Alphaviruses and Flaviviruses, are responsible for millions of human infections worldwide. The absence of specific antivirals for arbovirus infections underscores the urgent need for novel research to develop effective treatments. Natural products have emerged as promising candidates. Nordihydroguaiaretic acid (NDGA), a natural lignan predominantly found in Larrea spp., has shown antiviral activity against several viruses, including Dengue. This study aimed to investigate the antiviral potential of NDGA against West Nile virus (WNV), assessing its mechanism of action and cellular interactions. Using plaque-forming unit reduction and immunofluorescence assays in LLC-MK2 cells, we determine the reduction in viability of WNV viral particles at different times post-infection. The potential involvement of the sterol regulatory element-binding proteins (SREBP) and 5-lipoxygenase pathways in WNV infection was evaluated. Additionally, we analyzed the cytoskeleton integrity in treated cells. NDGA, had the greatest inhibitory effect on WNV replication when added 1 and 2 h post-viral internalization (PI), losing activity when added after 3 h PI, thus suggesting it targets early viral infection events. The SREBP pathway seems to be involved in the inhibition of WNV by NDGA, likely due to its lipogenic activity. Furthermore, the antiviral activity of NDGA could be related to its ability to modify the cytoskeleton of LLC-MK2 cells. These findings highlight NDGA potential as a therapeutic candidate against WNV and other flaviviruses. Plant metabolites are among the leading therapeutic resources globally. Further research is necessary to comprehensively assess the therapeutic promise of NDGA. Fil: Ghietto, Lucía María. Universidad Nacional de Córdoba. Facultad de Medicina. Instituto de Virología Dr. J. M. Vanella; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba; Argentina Fil: Lingua, Giuliana. Universidad Nacional de Córdoba. Facultad de Medicina. Instituto de Virología Dr. J. M. Vanella; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba; Argentina Fil: Gil, Pedro Ignacio. Universidad Nacional de Córdoba. Facultad de Medicina. Instituto de Virología Dr. J. M. Vanella; Argentina Fil: Aguilar, Juan Javier. Universidad Nacional de Córdoba. Facultad de Medicina. Instituto de Virología Dr. J. M. Vanella; Argentina Fil: Gomez, Tomás Isaac. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Unidad de Investigación y Desarrollo en Tecnología Farmacéutica. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Unidad de Investigación y Desarrollo en Tecnología Farmacéutica; Argentina. Universidad Nacional de Córdoba. Facultad de Medicina. Instituto de Virología Dr. J. M. Vanella; Argentina Fil: Marioni, Juliana. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Unidad de Investigación y Desarrollo en Tecnología Farmacéutica. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Unidad de Investigación y Desarrollo en Tecnología Farmacéutica; Argentina Fil: Núñez Montoya, Susana Carolina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Unidad de Investigación y Desarrollo en Tecnología Farmacéutica. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Unidad de Investigación y Desarrollo en Tecnología Farmacéutica; Argentina Fil: Konigheim, Brenda Salome. Universidad Nacional de Córdoba. Facultad de Medicina. Instituto de Virología Dr. J. M. Vanella; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba; Argentina Fil: Martinez, Florencia. Universidad Nacional de Córdoba. Facultad de Medicina. Instituto de Virología Dr. J. M. Vanella; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba; Argentina |
| description |
Mosquito-borne Arboviruses, including Alphaviruses and Flaviviruses, are responsible for millions of human infections worldwide. The absence of specific antivirals for arbovirus infections underscores the urgent need for novel research to develop effective treatments. Natural products have emerged as promising candidates. Nordihydroguaiaretic acid (NDGA), a natural lignan predominantly found in Larrea spp., has shown antiviral activity against several viruses, including Dengue. This study aimed to investigate the antiviral potential of NDGA against West Nile virus (WNV), assessing its mechanism of action and cellular interactions. Using plaque-forming unit reduction and immunofluorescence assays in LLC-MK2 cells, we determine the reduction in viability of WNV viral particles at different times post-infection. The potential involvement of the sterol regulatory element-binding proteins (SREBP) and 5-lipoxygenase pathways in WNV infection was evaluated. Additionally, we analyzed the cytoskeleton integrity in treated cells. NDGA, had the greatest inhibitory effect on WNV replication when added 1 and 2 h post-viral internalization (PI), losing activity when added after 3 h PI, thus suggesting it targets early viral infection events. The SREBP pathway seems to be involved in the inhibition of WNV by NDGA, likely due to its lipogenic activity. Furthermore, the antiviral activity of NDGA could be related to its ability to modify the cytoskeleton of LLC-MK2 cells. These findings highlight NDGA potential as a therapeutic candidate against WNV and other flaviviruses. Plant metabolites are among the leading therapeutic resources globally. Further research is necessary to comprehensively assess the therapeutic promise of NDGA. |
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