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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todo:paper_01663542_v95_n1_p37_Torres2023-10-03T15:03:53Z In vitro antiviral activity of dehydroepiandrosterone, 17 synthetic analogs and ERK modulators against herpes simplex virus type 1 Torres, N.I. Castilla, V. Bruttomesso, A.C. Eiras, J. Galagovsky, L.R. Wachsman, M.B. 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 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.. Fil:Torres, N.I. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. Fil:Castilla, V. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. Fil:Bruttomesso, A.C. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. Fil:Wachsman, M.B. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. JOUR info:eu-repo/semantics/openAccess http://creativecommons.org/licenses/by/2.5/ar http://hdl.handle.net/20.500.12110/paper_01663542_v95_n1_p37_Torres |
| institution |
Universidad de Buenos Aires |
| institution_str |
I-28 |
| repository_str |
R-134 |
| collection |
Biblioteca Digital - Facultad de Ciencias Exactas y Naturales (UBA) |
| topic |
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 |
| spellingShingle |
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 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 |
| topic_facet |
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 |
| description |
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.. |
| format |
JOUR |
| author |
Torres, N.I. Castilla, V. Bruttomesso, A.C. Eiras, J. Galagovsky, L.R. Wachsman, M.B. |
| author_facet |
Torres, N.I. Castilla, V. Bruttomesso, A.C. Eiras, J. Galagovsky, L.R. Wachsman, M.B. |
| author_sort |
Torres, N.I. |
| title |
In vitro antiviral activity of dehydroepiandrosterone, 17 synthetic analogs and ERK modulators against herpes simplex virus type 1 |
| title_short |
In vitro antiviral activity of dehydroepiandrosterone, 17 synthetic analogs and ERK modulators against herpes simplex virus type 1 |
| title_full |
In vitro antiviral activity of dehydroepiandrosterone, 17 synthetic analogs and ERK modulators against herpes simplex virus type 1 |
| title_fullStr |
In vitro antiviral activity of dehydroepiandrosterone, 17 synthetic analogs and ERK modulators against herpes simplex virus type 1 |
| title_full_unstemmed |
In vitro antiviral activity of dehydroepiandrosterone, 17 synthetic analogs and ERK modulators against herpes simplex virus type 1 |
| title_sort |
in vitro antiviral activity of dehydroepiandrosterone, 17 synthetic analogs and erk modulators against herpes simplex virus type 1 |
| url |
http://hdl.handle.net/20.500.12110/paper_01663542_v95_n1_p37_Torres |
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