title: Antiviral action of synthetic stigmasterol derivatives on herpes simplex virus replication in nervous cells in vitro.
abstract: Polyfunctionalized stigmasterol derivatives, (22S,23S)-22,23-dihydroxystigmast-4-en-3-one (compound 1) and (22S,23S)-3β-bromo-5α,22,23-trihydroxystigmastan-6-one (compound 2), inhibit herpes simplex virus type 1 (HSV-1) replication and spreading in human epithelial cells derived from ocular tissues. Both compounds reduce the incidence and severity of lesions in a murine model of herpetic stromal keratitis when administered in different treatment modalities. Since encephalitis caused by HSV-1 is another immunopathology of viral origin, we evaluate here the antiviral effect of both compounds on HSV-1 infected nervous cell lines as well as their anti-inflammatory action. We found that both stigmasterol derivatives presented low cytotoxicity in the three nervous cell lines assayed. Regarding the antiviral activity, in all cases both compounds prevented HSV-1 multiplication when added after infection, as well as virus propagation. Additionally, both compounds were able to hinder interleukin-6 and Interferon-gamma secretion induced by HSV-1 infection in Neuro-2a cells. We conclude that compounds 1 and 2 have exerted a dual antiviral and anti-inflammatory effect in HSV-1 infected nervous cell lines, which makes them interesting molecules to be further studied.
authors.affiliation: Laboratorio de Virología, Departamento de Química Biológica, IQUIBICEN, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Pabellón 2, 4to. Piso, Intendente Güiraldes 2160, Ciudad Universitaria, C1428EGA Buenos Aires, Argentina.
authors.forename: Erina
authors.initials: E
authors.lastname: Petrera
authors.affiliation: Laboratorio de Virología, Departamento de Química Biológica, IQUIBICEN, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Pabellón 2, 4to. Piso, Intendente Güiraldes 2160, Ciudad Universitaria, C1428EGA Buenos Aires, Argentina.
authors.forename: Analía G
authors.initials: AG
authors.lastname: Níttolo
authors.affiliation: Laboratorio de Virología, Departamento de Química Biológica, IQUIBICEN, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Pabellón 2, 4to. Piso, Intendente Güiraldes 2160, Ciudad Universitaria, C1428EGA Buenos Aires, Argentina.
authors.forename: Laura E
authors.initials: LE
authors.lastname: Alché
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology; D000998:Antiviral Agents / Q000494:pharmacology*; D002460:Cell Line; D002522:Chlorocebus aethiops; D002778:Cholestanones / Q000494:pharmacology*; D004847:Epithelial Cells / Q000187:drug effects / Q000378:metabolism; D018259:Herpesvirus 1, Human / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D007249:Inflammation / Q000188:drug therapy / Q000378:metabolism; D007371:Interferon-gamma / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D051379:Mice; D013265:Stigmasterol / Q000031:analogs & derivatives* / Q000494:pharmacology*; D014709:Vero Cells / Q000187:drug effects; D014779:Virus Replication / Q000187:drug effects*
chemical_list: C581395:22,23-dihydroxystigmast-4-en-3-one; C493970:3-bromo-5,22,23-trihydroxystigmastan-6-one; D000893:Anti-Inflammatory Agents; D000998:Antiviral Agents; D002778:Cholestanones; D015850:Interleukin-6; D007371:Interferon-gamma; D013265:Stigmasterol