title: In vitro antiviral activity of dehydroepiandrosterone, 17 synthetic analogs and ERK modulators against herpes simplex virus type 1.
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.
authors.affiliation: 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.
authors.forename: Nicolás I
authors.initials: NI
authors.lastname: Torres
authors.forename: Viviana
authors.initials: V
authors.lastname: Castilla
authors.forename: Andrea C
authors.initials: AC
authors.lastname: Bruttomesso
authors.forename: Javier
authors.initials: J
authors.lastname: Eiras
authors.forename: Lydia R
authors.initials: LR
authors.lastname: Galagovsky
authors.forename: Mónica B
authors.initials: MB
authors.lastname: Wachsman
mesh_terms: D000818:Animals; D000998:Antiviral Agents / Q000737:chemistry* / Q000494:pharmacology*; D002522:Chlorocebus aethiops; D003687:Dehydroepiandrosterone / Q000031:analogs & derivatives* / Q000494:pharmacology*; D018259:Herpesvirus 1, Human / Q000187:drug effects* / Q000502:physiology*; D008826:Microbial Sensitivity Tests; D050296:Microbial Viability / Q000187:drug effects; D014709:Vero Cells; D019562:Viral Load; D014764:Viral Proteins / Q000037:antagonists & inhibitors; D014779:Virus Replication / Q000187:drug effects*
chemical_list: D000998:Antiviral Agents; D014764:Viral Proteins; D003687:Dehydroepiandrosterone