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.
D000818:Animals; D000998:Antiviral Agents / Q000627:therapeutic use*; D047630:Depsipeptides; D005260:Female; D006561:Herpes Simplex / Q000188:drug therapy*; D008297:Male; D051379:Mice; D008812:Mice, Hairless; D008813:Mice, Inbred ICR; D010456:Peptides, Cyclic / Q000627:therapeutic use; D012672:Semliki forest virus; D013997:Time Factors; D014036:Togaviridae Infections / Q000188:drug therapy
D000998:Antiviral Agents; D047630:Depsipeptides; D010456:Peptides, Cyclic; C030051:didemnins