In vitro antiviral activity of dehydroepiandrosterone, 17 synthetic analogs and ERK modulators against herpes simplex virus type 1

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 i...

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Autor principal: Torres, N.I
Otros Autores: Castilla, V., Bruttomesso, A.C, Eiras, J., Galagovsky, L.R, Wachsman, M.B
Formato: Capítulo de libro
Lenguaje:Inglés
Publicado: 2012
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Acceso en línea:Registro en Scopus
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024 7 |2 cas  |a 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 
040 |a Scopus  |b spa  |c AR-BaUEN  |d AR-BaUEN 
030 |a ARSRD 
100 1 |a Torres, N.I. 
245 1 3 |a In vitro antiviral activity of dehydroepiandrosterone, 17 synthetic analogs and ERK modulators against herpes simplex virus type 1 
260 |c 2012 
270 1 0 |m Wachsman, M.B.; 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; email: wachsman@qb.fcen.uba.ar 
506 |2 openaire  |e Política editorial 
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520 3 |a 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..  |l eng 
536 |a Detalles de la financiación: Universidad de Buenos Aires, UBACYT 20020090200271 
536 |a Detalles de la financiación: Agencia Nacional de Promoción Científica y Tecnológica, PICT 00985/07 
536 |a Detalles de la financiación: This work was supported by Grants from the Universidad de Buenos Aires, UBA , UBACYT X 505 , UBACYT 20020090200271 and Agencia Nacional de Promoción Científica y Técnica (ANPCYT) PICT 00985/07 . The authors would like to thank Mrs. Claudia Iglesias for English and grammar corrections and Lic. Daniela Orquera for figure improvement. 
593 |a 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 
593 |a 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 
690 1 0 |a ANTIVIRAL 
690 1 0 |a DHEA 
690 1 0 |a DHEA ANALOGS 
690 1 0 |a ERK 
690 1 0 |a HERPES SIMPLEX VIRUS 
690 1 0 |a 16ALPHA BROMO 17,17 ETHYLENDIOXY 5ALPHA ANDROSTAN 3BETA OL 
690 1 0 |a 16ALPHA BROMO 17,17 ETHYLENDIOXY 5ALPHA ANDROSTAN 3BETA YL ACETATE 
690 1 0 |a 16ALPHA BROMO 3BETA HYDROXYANDROST 5 EN 17 ONE 
690 1 0 |a 16ALPHA BROMOEPIANDROSTERONE 
690 1 0 |a 17 OXO 5ALPHA ANDROSTAN 3BETA YL ACETATE 
690 1 0 |a 17 OXO 5ALPHA ANDROSTAN 3BETA,16ALPHA DIYL DIACETATE 
690 1 0 |a 17 OXOANDROST 5 EN 3B,16ALPHA DIYL DIACETATE 
690 1 0 |a 17 OXOANDROST 5 EN 3B,16BETA YL DIACETATE 
690 1 0 |a 17 OXOANDROST 5 EN 3BETA YL ACETATE 
690 1 0 |a 17,17 ETHYLENDIOXY 5ALPHA ANDROST 15 EN 3BETA OL 
690 1 0 |a 17,17 ETHYLENDIOXY 5ALPHA ANDROSTAN 3BETA YL ACETATE 
690 1 0 |a 17,17 ETHYLENDIOXYANDROST 5 EN 3B YL ACETATE 
690 1 0 |a 17,17 ETHYLENDIOXYANDROST 5 EN 3BETA OL 
690 1 0 |a 3BETA HYDROXY 5ALPHA ANDROST 15 EN 17 ONE 
690 1 0 |a 3BETA,15ALPHA DIHYDROXY 5ALPHA ANDROSTAN 17 ONE 
690 1 0 |a 3BETA,15BETA DIHYDROXY 5ALPHA ANDROSTAN 17 ONE 
690 1 0 |a 3BETA,16ALPHA DIHYDROXY 5ALPHA ANDROSTAN 17 ONE 
690 1 0 |a 9 (2 HYDROXYETOXYMETYL)GUANINE 
690 1 0 |a ANISOMYCIN 
690 1 0 |a ANTIVIRUS AGENT 
690 1 0 |a EPIANDROSTERONE 
690 1 0 |a MITOGEN ACTIVATED PROTEIN KINASE 
690 1 0 |a MITOGEN ACTIVATED PROTEIN KINASE 1 
690 1 0 |a MITOGEN ACTIVATED PROTEIN KINASE INHIBITOR 
690 1 0 |a PHOSPHONOFORMIC ACID TRISODIUM SALT HEXAHYDRATE 
690 1 0 |a PRASTERONE 
690 1 0 |a RAF PROTEIN 
690 1 0 |a UNCLASSIFIED DRUG 
690 1 0 |a UO 126 
690 1 0 |a VIRUS PROTEIN 
690 1 0 |a ANIMAL CELL 
690 1 0 |a ANTIVIRAL ACTIVITY 
690 1 0 |a ARTICLE 
690 1 0 |a CONTROLLED STUDY 
690 1 0 |a DRUG INHIBITION 
690 1 0 |a DRUG SCREENING 
690 1 0 |a ENZYME PHOSPHORYLATION 
690 1 0 |a HERPES SIMPLEX VIRUS 1 
690 1 0 |a IN VITRO STUDY 
690 1 0 |a INHIBITION KINETICS 
690 1 0 |a NONHUMAN 
690 1 0 |a PRIORITY JOURNAL 
690 1 0 |a PROTEIN SYNTHESIS INHIBITION 
690 1 0 |a VIRUS INHIBITION 
690 1 0 |a VIRUS LOAD 
690 1 0 |a ANIMALS 
690 1 0 |a ANTIVIRAL AGENTS 
690 1 0 |a CERCOPITHECUS AETHIOPS 
690 1 0 |a DEHYDROEPIANDROSTERONE 
690 1 0 |a HERPESVIRUS 1, HUMAN 
690 1 0 |a MICROBIAL SENSITIVITY TESTS 
690 1 0 |a MICROBIAL VIABILITY 
690 1 0 |a VERO CELLS 
690 1 0 |a VIRAL LOAD 
690 1 0 |a VIRAL PROTEINS 
690 1 0 |a VIRUS REPLICATION 
690 1 0 |a HERPES 
690 1 0 |a HUMAN HERPESVIRUS 1 
690 1 0 |a SIMPLEXVIRUS 
653 0 0 |a uo 126 
700 1 |a Castilla, V. 
700 1 |a Bruttomesso, A.C. 
700 1 |a Eiras, J. 
700 1 |a Galagovsky, L.R. 
700 1 |a Wachsman, M.B. 
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