In vitro anti-Junin virus activity of a peptide isolated from Melia azedarach L. leaves.

Meliacine, a peptide isolated from leaves of Melia azedarach L. inhibited the multiplication of Junin virus in Vero cells treated with the compound before infection (pre-treatment) or immediately after virus adsorption. Analysis of early events following infection demonstrated that meliacine blocks virus penetration by preventing the uncoating step. The addition of meliacine at different times after infection indicated that meliacine also interferes with the release of infectious particles to the extracellular medium and inhibits the low-pH-induced fusion of infected cells. Intracellular transport of viral glycoproteins to the cell membrane was not affected by meliacine, as revealed by immunofluorescence staining. Taken together, these results suggest that meliacine affects two events of the virus replicative cycle that require membrane fusion: uncoating and budding.

Antiviral activity of meliacine on the replication of a thymidine kinase-deficient mutant of Herpes simplex virus type 1 alone and in combination with acyclovir.

The anti-HSV-1 activity of meliacine (MA), a peptide isolated from leaves of Melia azedarach L., alone and in combination with acyclovir (ACV), was assayed against thymidine kinase-deficient (TK(-)) virus yields in vitro. MA alone proved to inhibit significantly TK(-) viral replication, whereas ACV was more potent than MA as an inhibitor of TK(+) replication. TK(-) and TK(+) synergistic inhibition by the combination of both agents was observed at concentrations that did not alter cell viability. The interaction between MA and ACV was quantitatively determined by calculating the combination index and plotting the data by the isobologram method. Besides, MA and ACV were able to suppress synergistically the antigen expression on HSV-I infected cells processed by an immunofluorescence assay. These in vitro findings suggest that combinations of MA and ACV at appropriate doses may provide an increased efficacy in inhibiting both TK(-) and TK(+) HSV-1 multiplication.

Estudio de la acción combinada de meliacina y foscarnet contra distintas cepas del virus herpes simplex tipo 1 empleando un modelo tridimensional / Evaluation of the antiviral activity of meliacine-foscarnet combination against different strains of herpes simplex virus type 1 by a three-dimensional model

Se estudió la actividad antiviral y citotóxica de varias combinaciones de meliacina y foscarnet in vitro con el objeto de identificar aquellas combinaciones que podrían presentar una mayor actividad antiviral sobre la multiplicación del virus herpes simplex tipo 1 (HSV-1) cepa F y la cepa deficiente en timidina quinasa (TK) B2006. En las condiciones ensayadas, la concentración efectiva 50 o/o (CE50) de meliacina contra HSV-1 (F) fue 12,5 mg/ml y 15,7 mg/ml para foscarnet; mientras que contra HSV-1 (B2006) fueron 3,1 mg/ml y 126 mg/ml respectivamente. El análisis de los resultados, utilizando un modelo tridimensional, reveló que algunas de las combinaciones inhiben en forma sinérgica la multiplicación de estas cepas en concentraciones que no reducen la viabilidad celular

Estudio de la acción combinada de meliacina y foscarnet contra distintas cepas del virus herpes simplex tipo 1 empleando un modelo tridimensional / Evaluation of the antiviral activity of meliacine-foscarnet combination against different strains of herpes simplex virus type 1 by a three-dimensional model

Se estudió la actividad antiviral y citotóxica de varias combinaciones de meliacina y foscarnet in vitro con el objeto de identificar aquellas combinaciones que podrían presentar una mayor actividad antiviral sobre la multiplicación del virus herpes simplex tipo 1 (HSV-1) cepa F y la cepa deficiente en timidina quinasa (TK) B2006. En las condiciones ensayadas, la concentración efectiva 50 o/o (CE50) de meliacina contra HSV-1 (F) fue 12,5 mg/ml y 15,7 mg/ml para foscarnet; mientras que contra HSV-1 (B2006) fueron 3,1 mg/ml y 126 mg/ml respectivamente. El análisis de los resultados, utilizando un modelo tridimensional, reveló que algunas de las combinaciones inhiben en forma sinérgica la multiplicación de estas cepas en concentraciones que no reducen la viabilidad celular (AU)

[Combined activity of meliacin and foscarnet against different strains of herpes simplex virus type 1 using a three-dimensional model]. / Estudio de la acción combinada de meliacina y foscarnet contra distintas cepas del virus herpes simplex tipo 1 empleando un modelo tridimensional.

We evaluated the in vitro antiviral activity of meliacin combined with foscarnet on the herpes simplex type 1 (HSV-1) strains F and B2006 (tk-) replication. The effective concentrations for 50% inhibition of HSV-1 (F) were 12.5 micrograms/ml for meliacin and 15.7 micrograms/ml for foscarnet, while for HSV-1 (B2006) were 3.1 micrograms/ml and 126 micrograms/ml, respectively. The data were analyzed for quantitation of synergism, additivity, and antagonism of multiple drug effect by the three-dimensional model. Some of the meliacin -foscarnet combinations synergistically inhibited HSV-1 (F) and HSV-1 (B2006) replication in vitro at concentrations that did not reduce cellular viability.