PERSONAL DE APOYO
FASCIO Mirta Liliana
artículos
Título:
Antiviral activity of an N-allyl acridone against dengue virus
Autor/es:
MARÍA B. MAZZUCCO; LAURA B. TALARICO; SEZEN VATANSEVER; ANA C. CARRO; MIRTA L. FASCIO; NORMA B. D´ACCORSO; CYBELE C. GARCÍA; ELSA B. DAMONTE
Revista:
JOURNAL OF BIOMEDICAL SCIENCE
Editorial:
BIOMED CENTRAL LTD
Referencias:
Lugar: Londres; Año: 2015 vol. 22 p. 1 - 12
ISSN:
1021-7770
Resumen:
Background: Dengue virus (DENV), a member of the family Flaviviridae, is at present the most widespreadcausative agent of a human viral disease transmitted by mosquitoes. Despite the increasing incidence of thispathogen, there are no antiviral drugs or vaccines currently available for treatment or prevention. In a previousscreening assay, we identified a group of N-allyl acridones as effective virus inhibitors. Here, the antiviral activityand mode of action targeted to viral RNA replication of one of the most active DENV-2 inhibitors was furthercharacterized.Results: The compound 10-allyl-7-chloro-9(10H)-acridone, designated 3b, was active to inhibit the in vitroinfection of Vero cells with the four DENV serotypes, with effective concentration 50% (EC50) values in the range12.5-27.1 μM, as determined by virus yield inhibition assays. The compound was also effective in human HeLacells. No cytotoxicity was detected at 3b concentrations up to 1000 μM. Mechanistic studies demonstrated thatvirus entry into the host cell was not affected, whereas viral RNA synthesis was strongly inhibited, as quantifiedby 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 DENVserotypes without a direct interaction with the host cell or the virion but interfering specifically with theintracellular virus multiplication. The mode of antiviral action for this acridone apparently involves the cellularenzyme inosine-monophospahe dehydrogenase together with another still unidentified target related to DENVRNA synthesis.