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 a lpha,22,23-pentahydroxystigmastan-6-one and (22R,23R,24S)-3 beta-bromo-5 al pha,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,stigma stan-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 we re 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 compound s were potent inhibitors of arenaviruses, (22S,23S,24S)-3 beta-bromo-5 alph a,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 antivi ral activity of brassinosteroid derivatives was not because of direct inact ivation; time-of-addition experiments suggested that a late step in HSV-1 m ultiplication was affected, whereas arenaviruses remained susceptible to th e compounds throughout the replicative cycle.