Inhibition of herpes simplex virus type 1 by the experimental immunosuppressive agent leflunomide

Background. Despite advances in antiviral chemotherapy, herpes simplex viru s type 1 (HSV-1), continues to complicate the clinical course of many allog raft recipients. We have previously demonstrated that the experimental immu nosuppressive agent leflunomide inhibits production of cytomegalovirus by i nterference with virion assembly. We test the hypothesis that this agent ex erts similar antiviral activity against HSV-1. Methods and Results. Plaque assay of virus yield from endothelial or Vero c ells after inoculation with each of four clinical HSV-1 isolates demonstrat ed a dose-dependent reduction of virus production in the presence of pharma cologic concentrations of A77 1726, the active metabolite of leflunomide. D NA dot blot and biochemical assay of viral DNA polymerase activity indicate d that A77 does not inhibit viral DNA synthesis. Rather, as visualized by t ransmission electron microscopic method, this agent seems to disrupt virion assembly by preventing nucleocapsid tegumentation. Conclusions. These findings, in demonstrating that leflunomide exerts antiv iral activity against HSV-1 by mechanisms similar to those we have previous ly shown with cytomegalovirus, imply that this agent may possess broad spec trum activity against other herpesviruses.