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

Shibro Shigeta, Shuichi Mori, Eiichi Kodama, Junko Kodama, Kazuo Takahashi, Toshihiro Yamase

Research output: Contribution to journalArticlepeer-review

108 Citations (Scopus)

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 {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 VIV and one VV and those of PM-1002 consisted of three VIV. 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.

Original languageEnglish
Pages (from-to)265-271
Number of pages7
JournalAntiviral Research
Volume58
Issue number3
DOIs
Publication statusPublished - 2003 May 1
Externally publishedYes

Keywords

  • Antiviral
  • Dengue fever virus
  • HIV
  • Polyoxometalate
  • RNA virus

ASJC Scopus subject areas

  • Pharmacology
  • Virology

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