Antiviral effect of brassinosteroids against herpes virus and arenaviruses

A natural brassinosteroid and a series of synthetic derivatives were found to be good inhibitors of herpes simplex virus type 1 (HSV-1) and arenavirus replication in cell culture. The synthetic compounds tested were analogues of the 24(S) ethylbrassinone. Compounds (22R,23R,24S)-2 alpha, 3 alpha,5 alpha,22,23-pentahydroxystigmastan-6-one and (22R,23R,24S)-3 beta-bromo-5 alpha,22,23-trihydroxy stigm-astan-6-one were cytotoxic at concentrations of 20-40 mu M. (22S,23S,24S)-2 alpha,3 alpha,22,23-tetrahydroxy-5 alpha,stigmastan-6-one, (22R,23R,24S)-3 beta-acetoxy-22,23-dihydroxy-5 alpha-cholestan-6-one, (22S,23S,24S)-3 beta-bromo-22,23-dihydroxy-5 alpha-chol-estan-6-one and (22S,23S,24S)-3 beta-bromo-5 alpha,22,23-trihydroxy-stigmastan-6-one were the most active of the series against HSV-1, with selectivity index (SI) values (CC50/EC50) ranging from 10.6 to 16.5. The majority of the compounds were potent inhibitors of arenaviruses, (22S,23S,24S)-3 beta-bromo-5 alpha,22,23-trihydroxy-stig-mastan-6-one being the most active, with SI values of 307.8 and 692.5 far Tacaribe and Junin viruses, respectively. The antiviral activity of brassinosteroid derivatives was not because of direct inactivation; time-of-addition experiments suggested that a late step in HSV-1 multiplication was affected, whereas arenaviruses remained susceptible to the compounds throughout the replicative cycle.