The synergistic effect of IFN-α and IFN-γ against HSV-2 replication in Vero cells is not interfered by the plant antiviral 1-cinnamoyl-3, 11-dihydroxymeliacarpin

BACKGROUND: Recent studies have shown that gamma interferon (IFN-γ) synergizes with IFN-α/β to inhibit herpes simplex virus type 1 (HSV-1) replication in vitro. Since IFN response represents an early host defense event against viral infection and the fact that treatment with meliacine, a plant antiviral, ameliorate the severity of the herpetic infection in female mice infected intravaginally with HSV-2, we wanted to investigate whether the administration of meliacine to HSV-2 infected mice could altered the homoestasis of IFNs host response. For this purpose we studied the effect of the compound 1-cinnamoyl-3,11-dihydroxymeliacarpin (CDM), which is the responsible for meliacine antiviral action, on the HSV-2 inhibition exerted by IFN α, IFN-γ or their combination. RESULTS: We have found that like HSV-1, IFN-γ synergizes with IFN-α to inhibit HSV-2 replication in Vero cells. While treatment with IFN-α or IFN-γ alone has weak antiviral action, HSV-2 plaque formation, viral replication and the onset of viral CPE in Vero cells are synergistically inhibited by interferon combination. In addition, CDM treatment contributes to protect cells from virus cytopathic effect and causes a strong inhibition of HSV-2 titer. Moreover, the presence of CDM for 2 h before IFN induction, during the 16 h induction period, only for 24 h after infection or during the complete IFN treatment period, reduces virus yields in an additive way without affecting IFN antiviral action. CONCLUSION: The results reported here indicated that the presence of CDM did not alter the antiviral activity of IFN-α, IFN-γ or the synergism exerted by their combination. As a result we can envision that the administration of CDM in vivo could not affect the biological activity of IFNs, which are so important mediators of the innate resistance to HSV-2 infection

El Paraíso (Mella azedarach L.): fuente de productos bioactivos

No disponibl

An antiviral principle present in a purified fraction from Melia azedarach L. leaf aqueous extract restrains Herpes simplex virus type 1 propagation

Meliacine (MA), an antiviral principle isolated from leaves of Melia azedarach L., exhibits potent antiviral activity against herpes simplex virus type 1 (HSV-1) by inhibiting specific infected-cell polypeptides (ICPs) produced late in infection. Some of these are involved in DNA synthesis and in the assembly of nucleocapsids. The present report provides additional evidence to elucidate the mode of action of MA against HSV-1. Time-of-addition experiments confirmed that MA affects a late event in the multiplication cycle of HSV-1. We showed that MA diminished the synthesis of viral DNA and inhibited the spread of infectious viral particles when HSV-1 that expresses -galactosidase activity was used. In addition, the lack of a protein with an apparent MW of 55 KD was detected in MA-treated cell extracts. Ultrastructural analysis of infected cells showed that, in the case of MA treatment, a large number of unenveloped nucleocapsids accumulated in the cytoplasm and a minor proportion of mature virus was found in cytoplasmic vesicles. These findings suggest that MA exerts an antiviral action on both the synthesis of viral DNA and the maturation and egress of HSV-1 during the infection of Vero cells.Fil: Alché, Laura E.. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Química Biológica. Laboratorio de Virología; ArgentinaFil: Barquero, Andrea Alejandra. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Química Biológica. Laboratorio de Virología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales; ArgentinaFil: Sanjuan, Norberto Aníbal. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de Buenos Aires. Facultad de Medicina. Departamento de Microbiología; ArgentinaFil: Coto, Celia Esther. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Química Biológica. Laboratorio de Virología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentin

Antiherpes virus activities of new 6-19 carbon-bridged steroids and some synthetic precursors

Three synthetic 6,19-carbon bridged steroids: 3β,20β -diacetyloxy-5α-chloro-19a(R)-hydroxy-6,19-methanopregnane, 3β,20β-diacetyloxy-5α-chloro-6,19-methanopregnane, 6,19-methanopregn-4-ene-3,20-dione and four synthetic precursors: 3β,20β-diacetyloxy-19-hydroxypregn-5-ene, 3β,20β -diacetyloxy-pregn-5-en-19-al, 3β,20β -diacetyloxy-19(E)-(methoxymethylidene)-pregn-5-ene and 20β -acetyloxy-3β-hydroxy-19(E)-(methoxymethylidene)-pregn-5-ene were tested against herpes virus replication in cell cultures. Several compounds were cytotoxic for stationary cells. Antiviral studies performed with all compounds against HSV-1 indicated a dose-dependent virus susceptibility with selectivity indexes (SI) values in the range 1.7-183.2. Selected compounds were also tested against HSV-2 and the SI values obtained were in the range of 31-273. Attempts to reveal the step of virus multiplication affected by pregnanes were performed with one compound. HSV-1 virus incubation with the compound did not alter the ability of virus particles to infect cells; moreover, neither virus adsorption nor penetration appeared to be affected. The drug must be present during at least the first 7 h of the virus cycle to inhibit more than 90% of virus production. All these results suggest that these novel molecules interfere with an intracellular step of virus multiplication, thus behaving like true antivirals.Fil: Petrera, Erina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Química Biológica. Laboratorio de Virología; ArgentinaFil: Joselevich, Maria. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Química Orgánica; ArgentinaFil: Ghini, Alberto Antonio. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Química Orgánica; ArgentinaFil: Burton, Gerardo. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Química Orgánica; ArgentinaFil: Coto, Celia Esther. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Química Biológica. Laboratorio de Virología; Argentin

Erratum to: Guidelines for the use and interpretation of assays for monitoring autophagy (3rd edition) (Autophagy, 12, 1, 1-222, 10.1080/15548627.2015.1100356

non present