Abstract:
Dengue virus (DENV) is the most prevalent mosquito borne viral pathogen worldwide. In this work we first evaluated the antiviral activity of natural and synthetic β-carbolines against DENV-2 multiplication in cell cultures. We determined that the natural β-carboline harmol and a synthetic harmine derivative, 9N-methylharmine, exhibit inhibitory effect on DENV-2 production without virucidal activity. The active compounds were inhibitory of all DENV serotypes, being DENV-2 the more susceptible to their antiviral action. The mode of action of 9N-methylharmine against DENV-2 was further explored. We determined that the derivative neither affects viral adsorption-internalization events nor viral RNA synthesis. The quantification of intracellular and extracellular viral genomes and infectious virus particles indicated that 9N-methylharmine would impair the maturation and release of virus particles to the extracellular medium affecting the spreading of the infection. Furthermore, we also determined that 9N-methylharmine antiviral activity is not related to the ability of the compound to downregulate p38 MAPK phosphorylation. © 2016 Elsevier B.V.
Registro:
Documento: |
Artículo
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Título: | Antiviral activity of natural and synthetic β-carbolines against dengue virus |
Autor: | Quintana, V.M.; Piccini, L.E.; Panozzo Zénere, J.D.; Damonte, E.B.; Ponce, M.A.; Castilla, V. |
Filiación: | Laboratorio de Virología, Departamento de Química Biológica, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires (UBA), Ciudad Universitaria, Pabellón 2, Piso 4, Ciudad Autónoma de Buenos Aires, C1428EGA, Argentina IQUIBICEN, Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET-UBA), Ciudad Universitaria, Buenos Aires, Argentina Ciclo Básico Común, Universidad de Buenos Aires (UBA), Ramos Mejía 841, Buenos Aires, Argentina
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Palabras clave: | 9n methylharmine; antivirus agent; beta carboline derivative; harmine; harmol; harmol acetate; harmol butyrate; harmol caprate; harmol propionate; harmol valerate; mitogen activated protein kinase 14; unclassified drug; virus RNA; antivirus agent; beta carboline; carboline derivative; harmine; harmol; mitogen activated protein kinase p38; adsorption; animal cell; antiviral activity; antiviral susceptibility; Article; cell culture; controlled study; dengue; Dengue virus 2; down regulation; drug effect; drug inhibition; drug screening; enzyme phosphorylation; nonhuman; priority journal; RNA synthesis; serotype; Vero cell line; virogenesis; virus genome; virus inhibition; virus particle; virus release; analogs and derivatives; animal; chemistry; Chlorocebus aethiops; Dengue virus; drug development; drug effects; genetics; human; phosphorylation; synthesis; virus replication; Animals; Antiviral Agents; Carbolines; Cercopithecus aethiops; Dengue Virus; Drug Discovery; Genome, Viral; Harmine; Humans; p38 Mitogen-Activated Protein Kinases; Phosphorylation; RNA, Viral; Vero Cells; Virus Replication |
Año: | 2016
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Volumen: | 134
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Página de inicio: | 26
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Página de fin: | 33
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DOI: |
http://dx.doi.org/10.1016/j.antiviral.2016.08.018 |
Título revista: | Antiviral Research
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Título revista abreviado: | Antiviral Res.
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ISSN: | 01663542
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CODEN: | ARSRD
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CAS: | harmine, 343-27-1, 442-51-3; harmol, 487-03-6; beta carboline, 244-63-3; Antiviral Agents; Carbolines; Harmine; harmol; norharman; p38 Mitogen-Activated Protein Kinases; RNA, Viral
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Registro: | https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_01663542_v134_n_p26_Quintana |
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Citas:
---------- APA ----------
Quintana, V.M., Piccini, L.E., Panozzo Zénere, J.D., Damonte, E.B., Ponce, M.A. & Castilla, V.
(2016)
. Antiviral activity of natural and synthetic β-carbolines against dengue virus. Antiviral Research, 134, 26-33.
http://dx.doi.org/10.1016/j.antiviral.2016.08.018---------- CHICAGO ----------
Quintana, V.M., Piccini, L.E., Panozzo Zénere, J.D., Damonte, E.B., Ponce, M.A., Castilla, V.
"Antiviral activity of natural and synthetic β-carbolines against dengue virus"
. Antiviral Research 134
(2016) : 26-33.
http://dx.doi.org/10.1016/j.antiviral.2016.08.018---------- MLA ----------
Quintana, V.M., Piccini, L.E., Panozzo Zénere, J.D., Damonte, E.B., Ponce, M.A., Castilla, V.
"Antiviral activity of natural and synthetic β-carbolines against dengue virus"
. Antiviral Research, vol. 134, 2016, pp. 26-33.
http://dx.doi.org/10.1016/j.antiviral.2016.08.018---------- VANCOUVER ----------
Quintana, V.M., Piccini, L.E., Panozzo Zénere, J.D., Damonte, E.B., Ponce, M.A., Castilla, V. Antiviral activity of natural and synthetic β-carbolines against dengue virus. Antiviral Res. 2016;134:26-33.
http://dx.doi.org/10.1016/j.antiviral.2016.08.018