Didemnins A and B. Effectiveness against cutaneous herpes simplex virus in mice

The antiviral activity of didemnin A and didemnin B against a lethal Semliki Forest virus (SFV) infection of mice and a cutaneous herpes type 1 infection in hairless mice was evaluated. Both compounds significantly decreased the severity of herpesvirus lesions if topical treatment with either didemnin A or didemnin B was started 2 days prior to infection. The survival rate was significantly greater (P = 0.03) in the didemnin B treated group than in controls. If initiation of treatment was delayed until 1 h after infection, no activity was obtained. The compounds were not active against cutaneous herpesvirus infection when injected intraperitoneally (i.p.). Didemnin B at concentrations as low as 1.5 micrograms, administered topically 3 times daily for 5 days, produced skin irritation. Eight times this level of didemnin A could be administered before similar toxicity was observed. The limited activity of didemnins A and B coupled with irritation at the treatment site limits their usefulness in treating cutaneous herpesvirus infection. Neither didemnin A nor B had significant activity in SFV-infected mice.