Antiherpes activity of glucoevatromonoside, a cardenolide isolated from a Brazilian cultivar of Digitalis lanata

Abstract

Cardiac glycosides, known ligands of the sodium pump, are widely used in the treatment of heart failure, such as digoxin and digitoxin. Besides this important activity, other biological activities, such as the antiviral activity, have been described for this group. HSV are responsible for many infections of oral, ocular and genital regions. Treatment with nucleoside analogs such as acyclovir is effective in most cases; however drug-resistance may arise due to prolonged treatment mainly in immunocompromised individuals. In this study, an antiherpes screening was performed with 65 cardenolide derivatives obtained from different sources, and one natural cardenolide, glucoevatromonoside, inhibited HSV-1 and HSV-2 replication at very low concentrations. This cardenolide showed viral inhibitory effects if added up to 12h p.i. and these effects appear to take place by the inhibition of viral proteins synthesis (ICP27, U(L)42, gB, gD), the blockage of virus release and the reduction of viral cell-to-cell spread. This compound also showed synergistic antiviral effects with acyclovir and anti-Na(+)K(+)ATPase activity, suggesting that cellular electrochemical gradient alterations might be involved in the mechanism of viral inhibition. These results suggest that cardenolides might be promising for future antiviral drug design.

Antiherpes evaluation of soybean isoflavonoids

“…A time-of-addition study was performed using a virus yield reduction assay as reported by Silva et al with minor modifications [27]. Briefly, confluent Vero or GMK AH1 cell monolayers were inoculated with 100 PFU of HSV-1 (KOS strain) per well and incubated at 37°C for 1 h. After removing viruses, cells were maintained at 37°C and treated with genistein (40 lM), coumestrol (40 lM) or ACV (20 lM) at 1, 2, 3, 4, 6, 8, 10, 12, 16, 18 and 24 h postinfection (p.i.).…”

“…Subsequently, the potential antiherpes activity was evaluated using a plaque number reduction assay as described previously by Silva et al [27]. Confluent monolayers of Vero or GMK AH1 cells were infected with 100 PFU per well of HSV-1 (KOS and 29R strains) or HSV-2 (strain 333), respectively, for 1 h at 37°C.…”

“…This assay was conducted as described by Silva et al [27]. Mixtures of genistein or coumestrol, at different concentrations, were incubated with 4 9 10 4 PFU of HSV-1 (KOS and 29R strains) or HSV-2 (strain 333) in serum-free MEM for 15 min at 37°C.…”

“…Adsorption and penetration inhibition assays were performed following the procedures described by Silva et al [27]. In the adsorption assay, pre-chilled Vero or GMK AH1 cell monolayers were exposed to 100 PFU per well of HSV-1 (KOS and 29R strains) or HSV-2 (strain 333) in the presence or absence of the samples.…”

“…The effect of samples on HSV cell-to-cell spread was investigated as described by Silva et al and Bertol et al [27,28]. Results were obtained by analysis of the images of 20 viral plaques formed in the absence (viral control) or the presence of different concentrations of each sample.…”