Arenavirus chemotherapy--retrospect and prospect

Two groups of compounds, identifiable by structural similarity, have been found to interfere with the in vitro replication of arenaviruses. All 4 members of the benzimidazole group contain dipolar fused benzene and 5-membered nitrogen-containing rings and share potential chelating ability through the different bidentate structures formed with their side-chains. The biological activity of one of these compounds, metisazone, has been shown to depend on the presence of divalent metals of the first transition series, Cu(++) being the most effective. Furthermore, whereas metisazone inactivates cell-free virus, two other members of the group, HBB and 1,2-bis(5-methoxy-1H-benzimidazol-2-yl)-1,2-ethanediol, act intracellularly. The site of action of the fourth member, SKF 30097, is not known. Using murine lymphocytic choriomeningitis infections as an in vivo model, the bisbenzimidazole derivative has been found to increase life-span without interfering with virus replication. Medication with SKF 30097 or metisazone and copper (2(+)) sulfate did not significantly or reproducibly change the expected day of death of the animals. The amantadine compounds of the second group have unusual symmetric structures with a 10-carbon cage. The parent compound acts intracellularly, while the site of action of an octachloro derivative is not known. Medication with the parent compound, but not the derivative, shortened the interval between LCM infection and death of the mouse. Tissue culture and animal screening of the many available derivatives in these two groups may uncover compounds more efficacious than those already examined.