Antiviral activity of natural and synthetic β-carbolines against dengue virus
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 de...
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todo:paper_01663542_v134_n_p26_Quintana2023-10-03T15:03:49Z Antiviral activity of natural and synthetic β-carbolines against dengue virus Quintana, V.M. Piccini, L.E. Panozzo Zénere, J.D. Damonte, E.B. Ponce, M.A. Castilla, V. 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 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. Fil:Damonte, E.B. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. Fil:Castilla, V. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. JOUR info:eu-repo/semantics/openAccess http://creativecommons.org/licenses/by/2.5/ar http://hdl.handle.net/20.500.12110/paper_01663542_v134_n_p26_Quintana |
| institution |
Universidad de Buenos Aires |
| institution_str |
I-28 |
| repository_str |
R-134 |
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Biblioteca Digital - Facultad de Ciencias Exactas y Naturales (UBA) |
| topic |
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 |
| spellingShingle |
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 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 |
| topic_facet |
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 |
| description |
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. |
| format |
JOUR |
| author |
Quintana, V.M. Piccini, L.E. Panozzo Zénere, J.D. Damonte, E.B. Ponce, M.A. Castilla, V. |
| author_facet |
Quintana, V.M. Piccini, L.E. Panozzo Zénere, J.D. Damonte, E.B. Ponce, M.A. Castilla, V. |
| author_sort |
Quintana, V.M. |
| title |
Antiviral activity of natural and synthetic β-carbolines against dengue virus |
| title_short |
Antiviral activity of natural and synthetic β-carbolines against dengue virus |
| title_full |
Antiviral activity of natural and synthetic β-carbolines against dengue virus |
| title_fullStr |
Antiviral activity of natural and synthetic β-carbolines against dengue virus |
| title_full_unstemmed |
Antiviral activity of natural and synthetic β-carbolines against dengue virus |
| title_sort |
antiviral activity of natural and synthetic β-carbolines against dengue virus |
| url |
http://hdl.handle.net/20.500.12110/paper_01663542_v134_n_p26_Quintana |
| work_keys_str_mv |
AT quintanavm antiviralactivityofnaturalandsyntheticbcarbolinesagainstdenguevirus AT piccinile antiviralactivityofnaturalandsyntheticbcarbolinesagainstdenguevirus AT panozzozenerejd antiviralactivityofnaturalandsyntheticbcarbolinesagainstdenguevirus AT damonteeb antiviralactivityofnaturalandsyntheticbcarbolinesagainstdenguevirus AT poncema antiviralactivityofnaturalandsyntheticbcarbolinesagainstdenguevirus AT castillav antiviralactivityofnaturalandsyntheticbcarbolinesagainstdenguevirus |
| _version_ |
1807324061066330112 |