S, indicating that it protects cells from damage by allowing timeS, indicating that it protects

S, indicating that it protects cells from damage by allowing time
S, indicating that it protects cells from damage by allowing time for cellular DNA damage repair to occur [27]. In addition to their individual protective potentials, the safe concentrations of each compound were determined in Huh7.5 cells. To accomplish this, the in vitro toxicities of the quinic acid derivatives were determinedThe quinic acid derivative 3,5-dicaffeoyl-muco-quinic acid has been shown to impair HIV integrase activity and inhibit viral replication in vitro [31]. Quinic, chlorogenic and caffeic acids exhibited anti-HBV activity in vitro in HepG2.2.15 cells. Crude extracts of regular PubMed ID:https://www.ncbi.nlm.nih.gov/pubmed/29069523 and decaffeinated coffee also inhibited HBV replication [19]. Additionally, 3,5-dicaffeoylquinic acid exhibited specific activity against respiratory syncytial virus (RSV). However, this compound was not able to inhibit influenza A and B subtypes or herpes simplex 1 and 2 [32]. It is notable that, to the best of our knowledge, the current study is the first to evaluate the activity of quinic acid derivatives against flavivirus replication. When screened in Huh7.5 cells using an in situ ELISA assay [33], two of the quinic acid derivatives, called SB 202190 side effects compounds 2 and 10, that were included in this study demonstrated anti-dengue virus activity at varying levels by reducing cell infectivity for all four dengue serotypes (Figs. 1 and 2). These data suggest that the presence of a lipophilic chain could contribute for the observed antiviral activity, as the compounds that did not possess this moiety were either less active or not active. To confirm the antiviral activity of compounds 2 and 10, PubMed ID:https://www.ncbi.nlm.nih.gov/pubmed/25962748 a flow cytometry assay was employed [34]. Data from FACS analysis confirmed that these compounds were able to reduce the percentage of cells infected with DENV (Fig. 2a). Furthermore, a titration of culture supernatants led to a notable reduction in virus titers (Fig. 2b), which corroborated the previous results. The concentration-response curves starting from the NTCs of compounds 2 and 10 showed different SIs for each dengue virus serotype (Table 2 and Additional file 1: Figure S1).Dengue virus replication is impaired by compounds 2 andAfter confirming the antiviral activity of compounds 2 and 10, we aimed to define which stage(s) of the viralZanello et al. Virology Journal (2015) 12:Page 3 ofTable 1 Molecular structures of quinic acid derivatives and cytotoxicity evaluations in Huh7.5 cellsCC50: cytotoxic concentration in 50 of cells NTC: non-toxic concentration in Huh7.5 cells NT: not-testedbaZanello et al. Virology Journal (2015) 12:Page 4 ofFig. 1 Antiviral screening. Huh7.5 cells were infected and treated during and after infection. After 72 h, the results from the in situ ELISA assay indicated the most promising substances (*p < 0.05 compared to DENV control). Data represent the mean ?standard error (SE) from three independent experiments (*p < 0.05 compared to DENV control)infection cycle was being affected by these compounds. First, virucidal effects were assessed as previously described [35], as it has been demonstrated that dicaffeoylquinic acid exhibited a virucidal effect against RSV at high concentrations that was dependent on temperature [36]. The results indicated that the compounds did not destroy viral particles, as demonstrated by the amplification of RNA after RNase treatment (Fig. 3). Furthermore, we evaluated whether the compounds could affect the early steps of viral infection in host cells. The treatment of cells with compounds 2 and 10 w.