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Mazzucco, M.B.; Talarico, L.B.; Vatansever, S.; Carro, A.C.; Fascio, M.L.; D'Accorso, N.B.; García, C.C.; Damonte, E.B. "Antiviral activity of an N-allyl acridone against dengue virus" (2015) Journal of Biomedical Science. 22(1)
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Abstract:

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% (EC50) 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.

Registro:

Documento: Artículo
Título:Antiviral activity of an N-allyl acridone against dengue virus
Autor:Mazzucco, M.B.; Talarico, L.B.; Vatansever, S.; Carro, A.C.; Fascio, M.L.; D'Accorso, N.B.; García, C.C.; Damonte, E.B.
Filiación:Departamento de Química Biológica, Facultad de Ciencias Exactas y Naturales, UBA, Piso 4, Buenos Aires, Pabellón, 1428, Argentina
Graduate School of Science and Engineering, Koc University, Rumelifener yolu, Istanbul, Sariyer, 34450, Turkey
IQUIBICEN-Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Buenos Aires, Argentina
Departamento de Química Orgánica, Facultad de Ciencias Exactas y Naturales, UBA, Pabellón 2, Piso 3, Buenos Aires, 1428, Argentina
Laboratorio de Reproducción y Metabolismo, Facultad de Medicina, UBA, Buenos Aires, 1121, Argentina
Fundación Infant, Buenos Aires, 1406, Argentina
Palabras clave: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
Año:2015
Volumen:22
Número:1
DOI: http://dx.doi.org/10.1186/s12929-015-0134-2
Título revista:Journal of Biomedical Science
Título revista abreviado:J. Biomed. Sci.
ISSN:10217770
CODEN:JBCIE
CAS:guanosine, 118-00-3; nicotinamide adenine dinucleotide, 53-84-9; Acridones; Allyl Compounds; Antiviral Agents; RNA, Viral
Registro:https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_10217770_v22_n1_p_Mazzucco

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Citas:

---------- APA ----------
Mazzucco, M.B., Talarico, L.B., Vatansever, S., Carro, A.C., Fascio, M.L., D'Accorso, N.B., García, C.C.,..., Damonte, E.B. (2015) . Antiviral activity of an N-allyl acridone against dengue virus. Journal of Biomedical Science, 22(1).
http://dx.doi.org/10.1186/s12929-015-0134-2
---------- CHICAGO ----------
Mazzucco, M.B., Talarico, L.B., Vatansever, S., Carro, A.C., Fascio, M.L., D'Accorso, N.B., et al. "Antiviral activity of an N-allyl acridone against dengue virus" . Journal of Biomedical Science 22, no. 1 (2015).
http://dx.doi.org/10.1186/s12929-015-0134-2
---------- MLA ----------
Mazzucco, M.B., Talarico, L.B., Vatansever, S., Carro, A.C., Fascio, M.L., D'Accorso, N.B., et al. "Antiviral activity of an N-allyl acridone against dengue virus" . Journal of Biomedical Science, vol. 22, no. 1, 2015.
http://dx.doi.org/10.1186/s12929-015-0134-2
---------- VANCOUVER ----------
Mazzucco, M.B., Talarico, L.B., Vatansever, S., Carro, A.C., Fascio, M.L., D'Accorso, N.B., et al. Antiviral activity of an N-allyl acridone against dengue virus. J. Biomed. Sci. 2015;22(1).
http://dx.doi.org/10.1186/s12929-015-0134-2