Broad spectrum anti-RNA virus activities of titanium and vanadium substituted polyoxotungstates

Seven polyoxotungstates substituted with vanadium or titanium atoms were examined for their activity against Flaviviridae (Dengue fever virus, DFV), Orthomyxoviridae (influenza virus type A, fluV-A), Paramyxoviridae (respiratory syncytial virus, RSV, parainfluenza virus type 2, PfluV-2 and canine distemper virus, CDV) and Lentiviridae (human immunodeficiency virus type 1, HIV-1) families. Among the seven polyoxotungstates examined, PM-43 {K₅[SiVW₁₁O₄₀]}, PM-47 {K₇[BVW₁₁O₄₀]}, and PM-1001 [K₁₀Na(VO)₃(SbW₉O₃₃) ₂]26H₂O contained vanadium. PM-1002 had the same core structure of (VO)₃(SbW₉O₃₃)₂ as PM-1001; however, three V atoms of PM-1001 consisted of two V^IV and one V^V and those of PM-1002 consisted of three V^IV. On the other hand, PM-518 {[Et₂NH₂]₇[PTi₂W ₁₀O₄₀]}, PM-520 [Pri₂NH₂]₅[PTiW₁₁O₄₀] and PM-523 [PriNH₃]₆H[PTi₂W₁₀O ₃₈(O₂)₂]H₂O all contained titanium. All compounds showed broad spectrum antiviral activity against all viruses examined except for PMs-43, -518 and -523 which did not exhibit inhibitory activity at ≥50μM against PfluV-2, CDV and DFV, respectively. All compounds were inhibitory against HIV replication at an EC₅₀ of less than 2.0μM. Among them, PMs-1001 and -1002 showed the most potent inhibition. The compounds were not toxic for MDCK, HEp-2 and Vero cells at a concentration of 200μM. For the exponentially growing MT-4 cells, the vanadium containing polyoxometalates (PMs-43, 47, 1001, 1002) showed toxicity at concentrations between 41 and 47μM. On the other hand, titanium containing polyoxometalates (PMs-518, -520, -523) were not toxic at 100μM. The mechanism of anti-HIV action of PM-1001 was analyzed: it affected the binding of HIV to the cell membrane and syncytium formation between HIV-infected and uninfected cells.