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Abstract:

In the present study the in vitro antiviral activity of dehydroepiandrosterone (DHEA) and 17 synthetic derivatives against herpes simplex type 1 (HSV-1) was determined. DHEA, epiandrosterone (EA), two synthetic DHEA analogs and three synthetic EA analogs showed a selective inhibitory effect on HSV in vitro multiplication. DHEA and E2, a synthetic derivative of EA, were not found to be virucidal to cell-free HSV-1 and did not impair virus adsorption or penetration. We determined that treatment with both compounds decreased viral protein synthesis. Moreover, inhibitory effect of DHEA and E2 on extracellular viral titer was stronger than the inhibition found on total viral infectivity, suggesting that the antiherpetic activity of these compounds may also be in part due to an inhibition in virus formation and release.Since DHEA is a known Raf/MEK/ERK signaling pathway activator, we studied the role of this pathway on HSV-1 infection. ERK1/2 phosphorylation was stimulated in HSV-1 infected cultures. UO126, a Raf/MEK/ERK signaling pathway inhibitor, impaired viral multiplication, while anisomycin, an activator of this pathway, enhanced it.Treatment with DHEA 6. h before infection enhanced HSV-1 multiplication. On the contrary, pre-treatment with E2, which does not modulate Raf/MEK/ERK signaling pathway, did not produce an increase of viral replication. Taking together these results, the antiviral activity of DHEA seems to occur via a mechanism independent of its ability to modulate ERK phosphorylation. © 2012 Elsevier B.V..

Registro:

Documento: Artículo
Título:In vitro antiviral activity of dehydroepiandrosterone, 17 synthetic analogs and ERK modulators against herpes simplex virus type 1
Autor:Torres, N.I.; Castilla, V.; Bruttomesso, A.C.; Eiras, J.; Galagovsky, L.R.; Wachsman, M.B.
Filiación:Laboratorio de Virología, Departamento de Química Biológica, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Ciudad Universitaria, Pabellón 2, Piso 4, 1428 Buenos Aires, Argentina
Departamento de Química Orgánica y UMYMFOR, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Ciudad Universitaria, Pabellón 2, Piso 4, 1428 Buenos Aires, Argentina
Palabras clave:Antiviral; DHEA; DHEA analogs; ERK; Herpes simplex virus; 16alpha bromo 17,17 ethylendioxy 5alpha androstan 3beta ol; 16alpha bromo 17,17 ethylendioxy 5alpha androstan 3beta yl acetate; 16alpha bromo 3beta hydroxyandrost 5 en 17 one; 16alpha bromoepiandrosterone; 17 oxo 5alpha androstan 3beta yl acetate; 17 oxo 5alpha androstan 3beta,16alpha diyl diacetate; 17 oxoandrost 5 en 3b,16alpha diyl diacetate; 17 oxoandrost 5 en 3b,16beta yl diacetate; 17 oxoandrost 5 en 3beta yl acetate; 17,17 ethylendioxy 5alpha androst 15 en 3beta ol; 17,17 ethylendioxy 5alpha androstan 3beta yl acetate; 17,17 ethylendioxyandrost 5 en 3b yl acetate; 17,17 ethylendioxyandrost 5 en 3beta ol; 3beta hydroxy 5alpha androst 15 en 17 one; 3beta,15alpha dihydroxy 5alpha androstan 17 one; 3beta,15beta dihydroxy 5alpha androstan 17 one; 3beta,16alpha dihydroxy 5alpha androstan 17 one; 9 (2 hydroxyetoxymetyl)guanine; anisomycin; antivirus agent; epiandrosterone; mitogen activated protein kinase; mitogen activated protein kinase 1; mitogen activated protein kinase inhibitor; phosphonoformic acid trisodium salt hexahydrate; prasterone; Raf protein; unclassified drug; uo 126; virus protein; animal cell; antiviral activity; article; controlled study; drug inhibition; drug screening; enzyme phosphorylation; Herpes simplex virus 1; in vitro study; inhibition kinetics; nonhuman; priority journal; protein synthesis inhibition; virus inhibition; virus load; Animals; Antiviral Agents; Cercopithecus aethiops; Dehydroepiandrosterone; Herpesvirus 1, Human; Microbial Sensitivity Tests; Microbial Viability; Vero Cells; Viral Load; Viral Proteins; Virus Replication; Herpes; Human herpesvirus 1; Simplexvirus
Año:2012
Volumen:95
Número:1
Página de inicio:37
Página de fin:48
DOI: http://dx.doi.org/10.1016/j.antiviral.2012.05.002
Título revista:Antiviral Research
Título revista abreviado:Antiviral Res.
ISSN:01663542
CODEN:ARSRD
CAS:anisomycin, 22862-76-6; epiandrosterone, 481-29-8; mitogen activated protein kinase, 142243-02-5; mitogen activated protein kinase 1, 137632-08-7; prasterone, 53-43-0; Antiviral Agents; Dehydroepiandrosterone, 53-43-0; Viral Proteins
Registro:https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_01663542_v95_n1_p37_Torres

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Citas:

---------- APA ----------
Torres, N.I., Castilla, V., Bruttomesso, A.C., Eiras, J., Galagovsky, L.R. & Wachsman, M.B. (2012) . In vitro antiviral activity of dehydroepiandrosterone, 17 synthetic analogs and ERK modulators against herpes simplex virus type 1. Antiviral Research, 95(1), 37-48.
http://dx.doi.org/10.1016/j.antiviral.2012.05.002
---------- CHICAGO ----------
Torres, N.I., Castilla, V., Bruttomesso, A.C., Eiras, J., Galagovsky, L.R., Wachsman, M.B. "In vitro antiviral activity of dehydroepiandrosterone, 17 synthetic analogs and ERK modulators against herpes simplex virus type 1" . Antiviral Research 95, no. 1 (2012) : 37-48.
http://dx.doi.org/10.1016/j.antiviral.2012.05.002
---------- MLA ----------
Torres, N.I., Castilla, V., Bruttomesso, A.C., Eiras, J., Galagovsky, L.R., Wachsman, M.B. "In vitro antiviral activity of dehydroepiandrosterone, 17 synthetic analogs and ERK modulators against herpes simplex virus type 1" . Antiviral Research, vol. 95, no. 1, 2012, pp. 37-48.
http://dx.doi.org/10.1016/j.antiviral.2012.05.002
---------- VANCOUVER ----------
Torres, N.I., Castilla, V., Bruttomesso, A.C., Eiras, J., Galagovsky, L.R., Wachsman, M.B. In vitro antiviral activity of dehydroepiandrosterone, 17 synthetic analogs and ERK modulators against herpes simplex virus type 1. Antiviral Res. 2012;95(1):37-48.
http://dx.doi.org/10.1016/j.antiviral.2012.05.002