title: Broad spectrum anti-RNA virus activities of titanium and vanadium substituted polyoxotungstates.
abstract: 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 [K(5)[SiVW(11)O(40)]], PM-47 [K(7)[BVW(11)O(40)]], and PM-1001 [K(10)Na(VO)(3)(SbW(9)O(33))(2)]26H(2)O contained vanadium. PM-1002 had the same core structure of (VO)(3)(SbW(9)O(33))(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 [[Et(2)NH(2)](7)[PTi(2)W(10)O(40)]], PM-520 [Pri(2)NH(2)](5)[PTiW(11)O(40)] and PM-523 [PriNH(3)](6)H[PTi(2)W(10)O(38)(O(2))(2)]H(2)O 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 >/=50 microM against PfluV-2, CDV and DFV, respectively. All compounds were inhibitory against HIV replication at an EC(50) of less than 2.0 microM. 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 200 microM. For the exponentially growing MT-4 cells, the vanadium containing polyoxometalates (PMs-43, 47, 1001, 1002) showed toxicity at concentrations between 41 and 47 microM. On the other hand, titanium containing polyoxometalates (PMs-518, -520, -523) were not toxic at 100 microM. 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.
authors.affiliation: Department of Microbiology, Fukushima Medical University School of Medicine, 1 Hikarigaoka, 960-1295, Fukushima, Japan. sshigeta@fmu.ac.jp
authors.forename: Shibro
authors.initials: S
authors.lastname: Shigeta
authors.forename: Shuichi
authors.initials: S
authors.lastname: Mori
authors.forename: Eiichi
authors.initials: E
authors.lastname: Kodama
authors.forename: Junko
authors.initials: J
authors.lastname: Kodama
authors.forename: Kazuo
authors.initials: K
authors.lastname: Takahashi
authors.forename: Toshihiro
authors.initials: T
authors.lastname: Yamase
mesh_terms: D000818:Animals; D000998:Antiviral Agents / Q000737:chemistry / Q000494:pharmacology* / Q000633:toxicity; D002460:Cell Line; D015497:HIV-1 / Q000187:drug effects / Q000502:physiology; D006801:Humans; D008826:Microbial Sensitivity Tests / Q000379:methods; D011108:Polymers / Q000737:chemistry / Q000494:pharmacology* / Q000633:toxicity; D012328:RNA Viruses / Q000145:classification / Q000187:drug effects* / Q000502:physiology; D014025:Titanium / Q000737:chemistry*; D017973:Tungsten Compounds / Q000737:chemistry / Q000494:pharmacology* / Q000633:toxicity; D014639:Vanadium / Q000737:chemistry*; D014779:Virus Replication / Q000187:drug effects
chemical_list: D000998:Antiviral Agents; D011108:Polymers; D017973:Tungsten Compounds; D014639:Vanadium; D014025:Titanium