POTENT INHIBITION OF RESPIRATORY SYNCYTIAL VIRUS BY POLYOXOMETALATES OF SEVERAL STRUCTURAL CLASSES

A series of polyoxometalates (POM) were synthesized and evaluated for anti-respiratory syncytial virus (RSV) activity. POM containing zircon ium, tungsten, silicon, platinum, niobium or germanium of a variety of structural types have been evaluated. Sixteen of the compounds had ve ry striking anti-RSV activity against a clinical isolate, Utah 89, wit h median effective concentration (EC(50)) values less than or equal to 3 mu M and selective indices > 80 as determined by viral cytopathic i nhibition effect, neutral red uptake and virus yield reduction assays. The EC(50) values for all three assays correlated very well (Pearson correlation coefficients > 0.90>. POM containing sodium cations were t otally inactive. Germanium-, niobium-, tin: and zirconium-containing c ompounds were found to be highly potent and selective. The antiviral a ctivity was not cell line-dependent. The median cytotoxic concentratio n (IC50) values were generally greater than 100 mu M. The compounds we re also comparably active against a known laboratory RSV strain, A2, a s well as other RSV strains. To detect any virus strain-specific inhib itory activity, seven POM were tested against other RSV strains; all w ere nearly equally inhibitory to the human virus strains, suggesting n o strain specificity. Timing studies suggested that these compounds we re most inhibitory during virus adsorption and penetration, although R SV. was still Significantly inhibited when the compound was added 3 h post-infection; which is considered well into the eclipse period. Thes e data suggest that these potent, non-toxic compounds should be furthe r studied as potential chemotherapeutic agents for treating RSV infect ions. (C) 1997 Elsevier Science B.V.