Anti-adenovirus activity of epiandrosterone and dehydroepiandrosterone derivatives.
BACKGROUND
Dehydroepiandrosterone (DHEA) exhibits a wide range of biological functions including antiviral activity. In this work, we present in vitro anti-adenovirus (AdV) activity of seven DHEA and twelve epiandrosterone (EA) analogues.


METHODS
The cytotoxic effect of the compounds was determined by the MTT assay and the antiviral activity by a virus yield inhibition assay. The mode of antiviral activity was examined using time-of-addition experiments, adsorption and internalization assays and Western blot analysis.


RESULTS
EA, DHEA, and two synthetic derivatives inhibit virus replication with selectivity indices ranging between 42 and 83. Virus adsorption and internalization are not the target of the inhibitory action; meanwhile, AdV protein synthesis was diminished in the presence of DHEA.


CONCLUSIONS
DHEA and some synthetic derivatives present antiviral activity similar to cidofovir, which was used as reference drug. These steroidal compounds adversely affect virus protein synthesis and viral mature particle formation.
Romanutti
Carina
C
Laboratorio de Virología, Departamento de Química Biológica, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Buenos Aires, Argentina.
Bruttomesso
Andrea C
AC
Castilla
Viviana
V
Galagovsky
Lydia R
LR
Wachsman
Mónica B
MB
D000256:Adenoviridae / Q000187:drug effects*; D000738:Androsterone / Q000031:analogs & derivatives / Q000494:pharmacology*; D000818:Animals; D000998:Antiviral Agents / Q000737:chemistry / Q000494:pharmacology*; D015153:Blotting, Western; D002522:Chlorocebus aethiops; D000077404:Cidofovir; D003596:Cytosine / Q000031:analogs & derivatives / Q000494:pharmacology; D003687:Dehydroepiandrosterone / Q000031:analogs & derivatives / Q000494:pharmacology*; D006801:Humans; D051379:Mice; D063065:Organophosphonates / Q000494:pharmacology; D014709:Vero Cells; D014764:Viral Proteins / Q000096:biosynthesis; D014779:Virus Replication / Q000187:drug effects
D000998:Antiviral Agents; D063065:Organophosphonates; D014764:Viral Proteins; D003687:Dehydroepiandrosterone; D003596:Cytosine; D000738:Androsterone; D000077404:Cidofovir