Antiviral activity of an N-allyl acridone against dengue virus

Background: Dengue virus (DENV), a member of the family Flaviviridae, is at present the most widespread causative agent of a human viral disease transmitted by mosquitoes. Despite the increasing incidence of this pathogen, there are no antiviral drugs or vaccines currently available for treatment or...

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Autores principales:	Talarico, Laura Beatriz, Fascio, Mirta Liliana, D'Accorso, Norma Beatriz, García, Cybele Carina, Damonte, Elsa Beatriz
Publicado:	2015
Materias:	Acridone Antiviral Dengue virus Re-emerging infection RNA synthesis 10 allyl 7 chloro 9(10h) acridone acridone derivative antivirus agent cell enzyme cell protein guanosine nicotinamide adenine dinucleotide unclassified drug virus protein virus RNA allyl compound animal cell antiviral activity antiviral susceptibility Article cell metabolism cell viability concentration response controlled study dengue Dengue virus 1 Dengue virus 2 Dengue virus 3 Dengue virus 4 drug efficacy drug mechanism female HeLa cell line host cell human human cell hydrogen bond in vitro study molecular docking nonhuman priority journal protein conformation protein expression real time polymerase chain reaction reverse transcription polymerase chain reaction RNA replication Vero cell line virion virogenesis virus attachment virus entry virus infectivity virus inhibition virus replication drug effects metabolism Flaviviridae Acridones Allyl Compounds Antiviral Agents Dengue Virus RNA, Viral Virus Replication
Acceso en línea:	https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_10217770_v22_n1_p_Mazzucco http://hdl.handle.net/20.500.12110/paper_10217770_v22_n1_p_Mazzucco
Aporte de:	Biblioteca Digital - Facultad de Ciencias Exactas y Naturales (UBA) de Universidad de Buenos Aires

id	paper:paper_10217770_v22_n1_p_Mazzucco
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spelling	paper:paper_10217770_v22_n1_p_Mazzucco2023-06-08T16:00:03Z Antiviral activity of an N-allyl acridone against dengue virus Talarico, Laura Beatriz Fascio, Mirta Liliana D'Accorso, Norma Beatriz García, Cybele Carina Damonte, Elsa Beatriz Acridone Antiviral Dengue virus Re-emerging infection RNA synthesis 10 allyl 7 chloro 9(10h) acridone acridone derivative antivirus agent cell enzyme cell protein guanosine nicotinamide adenine dinucleotide unclassified drug virus protein virus RNA acridone derivative allyl compound antivirus agent animal cell antiviral activity antiviral susceptibility Article cell metabolism cell viability concentration response controlled study dengue Dengue virus Dengue virus 1 Dengue virus 2 Dengue virus 3 Dengue virus 4 drug efficacy drug mechanism female HeLa cell line host cell human human cell hydrogen bond in vitro study molecular docking nonhuman priority journal protein conformation protein expression real time polymerase chain reaction reverse transcription polymerase chain reaction RNA replication RNA synthesis Vero cell line virion virogenesis virus attachment virus entry virus infectivity virus inhibition virus replication Dengue virus drug effects metabolism Dengue virus Flaviviridae Acridones Allyl Compounds Antiviral Agents Dengue Virus RNA, Viral Virus Replication Background: Dengue virus (DENV), a member of the family Flaviviridae, is at present the most widespread causative agent of a human viral disease transmitted by mosquitoes. Despite the increasing incidence of this pathogen, there are no antiviral drugs or vaccines currently available for treatment or prevention. In a previous screening assay, we identified a group of N-allyl acridones as effective virus inhibitors. Here, the antiviral activity and mode of action targeted to viral RNA replication of one of the most active DENV-2 inhibitors was further characterized. Results: The compound 10-allyl-7-chloro-9(10H)-acridone, designated 3b, was active to inhibit the in vitro infection of Vero cells with the four DENV serotypes, with effective concentration 50% (EC<inf>50</inf>) values in the range 12.5-27.1 μM, as determined by virus yield inhibition assays. The compound was also effective in human HeLa cells. No cytotoxicity was detected at 3b concentrations up to 1000 μM. Mechanistic studies demonstrated that virus entry into the host cell was not affected, whereas viral RNA synthesis was strongly inhibited, as quantified by real time RT-PCR. The addition of exogenous guanosine together with 3b rescued only partially the infectivity of DENV-2. Conclusions: The acridone derivative 3b selectively inhibits the infection of Vero cells with the four DENV serotypes without a direct interaction with the host cell or the virion but interfering specifically with the intracellular virus multiplication. The mode of antiviral action for this acridone apparently involves the cellular enzyme inosine-monophospahe dehydrogenase together with another still unidentified target related to DENV RNA synthesis. © 2015 Mazzucco et al.; licensee BioMed Central. Fil:Talarico, L.B. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. Fil:Fascio, M.L. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. Fil:D'Accorso, N.B. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. Fil:García, C.C. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. Fil:Damonte, E.B. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. 2015 https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_10217770_v22_n1_p_Mazzucco http://hdl.handle.net/20.500.12110/paper_10217770_v22_n1_p_Mazzucco
institution	Universidad de Buenos Aires
institution_str	I-28
repository_str	R-134
collection	Biblioteca Digital - Facultad de Ciencias Exactas y Naturales (UBA)
topic	Acridone Antiviral Dengue virus Re-emerging infection RNA synthesis 10 allyl 7 chloro 9(10h) acridone acridone derivative antivirus agent cell enzyme cell protein guanosine nicotinamide adenine dinucleotide unclassified drug virus protein virus RNA acridone derivative allyl compound antivirus agent animal cell antiviral activity antiviral susceptibility Article cell metabolism cell viability concentration response controlled study dengue Dengue virus Dengue virus 1 Dengue virus 2 Dengue virus 3 Dengue virus 4 drug efficacy drug mechanism female HeLa cell line host cell human human cell hydrogen bond in vitro study molecular docking nonhuman priority journal protein conformation protein expression real time polymerase chain reaction reverse transcription polymerase chain reaction RNA replication RNA synthesis Vero cell line virion virogenesis virus attachment virus entry virus infectivity virus inhibition virus replication Dengue virus drug effects metabolism Dengue virus Flaviviridae Acridones Allyl Compounds Antiviral Agents Dengue Virus RNA, Viral Virus Replication
spellingShingle	Acridone Antiviral Dengue virus Re-emerging infection RNA synthesis 10 allyl 7 chloro 9(10h) acridone acridone derivative antivirus agent cell enzyme cell protein guanosine nicotinamide adenine dinucleotide unclassified drug virus protein virus RNA acridone derivative allyl compound antivirus agent animal cell antiviral activity antiviral susceptibility Article cell metabolism cell viability concentration response controlled study dengue Dengue virus Dengue virus 1 Dengue virus 2 Dengue virus 3 Dengue virus 4 drug efficacy drug mechanism female HeLa cell line host cell human human cell hydrogen bond in vitro study molecular docking nonhuman priority journal protein conformation protein expression real time polymerase chain reaction reverse transcription polymerase chain reaction RNA replication RNA synthesis Vero cell line virion virogenesis virus attachment virus entry virus infectivity virus inhibition virus replication Dengue virus drug effects metabolism Dengue virus Flaviviridae Acridones Allyl Compounds Antiviral Agents Dengue Virus RNA, Viral Virus Replication Talarico, Laura Beatriz Fascio, Mirta Liliana D'Accorso, Norma Beatriz García, Cybele Carina Damonte, Elsa Beatriz Antiviral activity of an N-allyl acridone against dengue virus
topic_facet	Acridone Antiviral Dengue virus Re-emerging infection RNA synthesis 10 allyl 7 chloro 9(10h) acridone acridone derivative antivirus agent cell enzyme cell protein guanosine nicotinamide adenine dinucleotide unclassified drug virus protein virus RNA acridone derivative allyl compound antivirus agent animal cell antiviral activity antiviral susceptibility Article cell metabolism cell viability concentration response controlled study dengue Dengue virus Dengue virus 1 Dengue virus 2 Dengue virus 3 Dengue virus 4 drug efficacy drug mechanism female HeLa cell line host cell human human cell hydrogen bond in vitro study molecular docking nonhuman priority journal protein conformation protein expression real time polymerase chain reaction reverse transcription polymerase chain reaction RNA replication RNA synthesis Vero cell line virion virogenesis virus attachment virus entry virus infectivity virus inhibition virus replication Dengue virus drug effects metabolism Dengue virus Flaviviridae Acridones Allyl Compounds Antiviral Agents Dengue Virus RNA, Viral Virus Replication
description	Background: Dengue virus (DENV), a member of the family Flaviviridae, is at present the most widespread causative agent of a human viral disease transmitted by mosquitoes. Despite the increasing incidence of this pathogen, there are no antiviral drugs or vaccines currently available for treatment or prevention. In a previous screening assay, we identified a group of N-allyl acridones as effective virus inhibitors. Here, the antiviral activity and mode of action targeted to viral RNA replication of one of the most active DENV-2 inhibitors was further characterized. Results: The compound 10-allyl-7-chloro-9(10H)-acridone, designated 3b, was active to inhibit the in vitro infection of Vero cells with the four DENV serotypes, with effective concentration 50% (EC<inf>50</inf>) values in the range 12.5-27.1 μM, as determined by virus yield inhibition assays. The compound was also effective in human HeLa cells. No cytotoxicity was detected at 3b concentrations up to 1000 μM. Mechanistic studies demonstrated that virus entry into the host cell was not affected, whereas viral RNA synthesis was strongly inhibited, as quantified by real time RT-PCR. The addition of exogenous guanosine together with 3b rescued only partially the infectivity of DENV-2. Conclusions: The acridone derivative 3b selectively inhibits the infection of Vero cells with the four DENV serotypes without a direct interaction with the host cell or the virion but interfering specifically with the intracellular virus multiplication. The mode of antiviral action for this acridone apparently involves the cellular enzyme inosine-monophospahe dehydrogenase together with another still unidentified target related to DENV RNA synthesis. © 2015 Mazzucco et al.; licensee BioMed Central.
author	Talarico, Laura Beatriz Fascio, Mirta Liliana D'Accorso, Norma Beatriz García, Cybele Carina Damonte, Elsa Beatriz
author_facet	Talarico, Laura Beatriz Fascio, Mirta Liliana D'Accorso, Norma Beatriz García, Cybele Carina Damonte, Elsa Beatriz
author_sort	Talarico, Laura Beatriz
title	Antiviral activity of an N-allyl acridone against dengue virus
title_short	Antiviral activity of an N-allyl acridone against dengue virus
title_full	Antiviral activity of an N-allyl acridone against dengue virus
title_fullStr	Antiviral activity of an N-allyl acridone against dengue virus
title_full_unstemmed	Antiviral activity of an N-allyl acridone against dengue virus
title_sort	antiviral activity of an n-allyl acridone against dengue virus
publishDate	2015
url	https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_10217770_v22_n1_p_Mazzucco http://hdl.handle.net/20.500.12110/paper_10217770_v22_n1_p_Mazzucco
work_keys_str_mv	AT talaricolaurabeatriz antiviralactivityofannallylacridoneagainstdenguevirus AT fasciomirtaliliana antiviralactivityofannallylacridoneagainstdenguevirus AT daccorsonormabeatriz antiviralactivityofannallylacridoneagainstdenguevirus AT garciacybelecarina antiviralactivityofannallylacridoneagainstdenguevirus AT damonteelsabeatriz antiviralactivityofannallylacridoneagainstdenguevirus
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Antiviral activity of an N-allyl acridone against dengue virus

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