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 journalArticle

104 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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