Two aromatic polycyclic diones hypericin and pseudohypericin have potent antiretroviral activity; these substances occur in plants of the Hypericum family. Both compounds are highly effective in preventing viral-induced manifestations that follow infections with a variety of retroviruses in vivo and in vitro. Pseudohypericin and hypericin probably interfere with viral infection and/or spread by direct

Administration of the aromatic polycyclic dione compounds hypericin or pseudohypericin to experimental animals provides protection from disease induced by retroviruses that give rise to acute, as well as slowly progressive, diseases. For example, survival from Friend virus-induced leukemia is significantly prolonged by both compounds, with hypericin showing the greater potency. Viremia induced by LP-BM5 murine immunodeficiency virus is markedly suppressed after infrequent dosage of either substance. These compounds affect the retroviral infection and replication cycle at least at two different points: (i) Assembly or processing of intact virions from infected cells was shown to be affected by hypericin. Electron microscopy of hypericin-treated, virusproducing cells revealed the production of particles containing immature or abnormally assembled cores, suggesting the compounds may interfere with processing of gag-encoded precursor polyproteins. The released virions contain no detectable activity of reverse transcriptase. (ii) Hypericin and pseudohypericin also directly inactivate mature and properly assembled retroviruses as determined by assays for reverse transcriptase and infectivity. Accumulating data from our laboratories suggest that these compounds inhibit retroviruses by unconventional mechanisms and that the potential therapeutic value of hypericin and pseudohypericin should be explored in diseases such as AIDS.We recently reported (1) that two naturally occurring polycyclic aromatic diones, hypericin and pseudohypericin, possess antiretroviral activity. The two compounds, which are derived from the plants of the Hypericum genus (St. Johnswort) (2-5), markedly suppress the spread of murine retrovirus infections both in vivo and in vitro (1). We have now compared the mechanisms of action and the therapeutic potentials of different doses of these agents in two murine retroviral systems. In the Friend virus system (6-8) the compounds can preclude the onset of acute Friend virusinduced erythroleukemia. In the other system a more slowly progressing, fatal form of murine immunodeficiency is induced by the LP-BM5 virus (9, 10); hypericin and pseudohypericin prevent development of significant viremia and minimize disease in mice infected with the LP-BM5 virus.