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Antiviral activity of an N-allyl acridone against dengue virus.

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.

journal_name

J Biomed Sci

journal_title

Journal of biomedical science

authors

Mazzucco MB,Talarico LB,Vatansever S,Carro AC,Fascio ML,D'Accorso NB,García CC,Damonte EB

doi

10.1186/s12929-015-0134-2

subject

Has Abstract

pub_date

2015-04-17 00:00:00

pages

29

eissn

1021-7770

issn

1423-0127

pii

10.1186/s12929-015-0134-2

journal_volume

22

pub_type

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