Anti-adenovirus activity of epiandrosterone and dehydroepiandrosterone derivatives

Abstract

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. Copyright © 2010 S. Karger AG, Basel.