Author:

Keywords:

Science & Technology, Life Sciences & Biomedicine, Biochemistry & Molecular Biology, Pharmacology & Pharmacy, Virology, HUMAN-IMMUNODEFICIENCY-VIRUS, HERPES-SIMPLEX VIRUS, ANTI-HIV COMPOUNDS, DEXTRAN SULFATE, HUMAN CYTOMEGALOVIRUS, SELECTIVE INHIBITORS, ENVELOPED VIRUSES, HEPARAN-SULFATE, VIRION BINDING, REPLICATION, 0304 Medicinal and Biomolecular Chemistry, 0601 Biochemistry and Cell Biology, 1117 Public Health and Health Services, 3404 Medicinal and biomolecular chemistry

Abstract:

A series of silicon-containing polyoxotungstates belonging to the 'Keggin-type' ('Keggin', 'Keggin sandwich') were evaluated for their antiviral activity against enveloped viruses (myxo-, herpes- and retroviruses). The compounds exhibited antiviral activity against influenza virus type A, respiratory syncytial virus (RSV), herpes simplex virus type-1 (HSV-1), type-2 (HSV-2), thymidine kinase-deficient (TK-) HSV-1, human cytomegalovirus (HCMV), human immunodeficiency virus type-1 (HIV-1) and type-2 (HIV-2) at concentrations that were well below their cytotoxic threshold. The 'Keggin' compound JM2815 (K5[Si-(TiCp)W11O39].12H2O) and the 'Keggin sandwich' compound JM1590 (K13[Ce(SiW11O39)2].26H2O) resulted in the highest selectivity indices against HIV-1 and HIV-2, and compound JM2820 ([Me3NH]8-[Si2Nb6W18O77]) was the most potent inhibitor of HSV and HCMV replication. These compounds proved active against HCMV and HSV when present during virus adsorption, and against influenza virus A and RSV when present after virus adsorption. Polyoxosilicotungstates inhibited the binding of radiolabelled HCMV particles to the cells at concentrations that were antivirally active, and the compounds were able to displace HCMV particles that were bound to a heparin-Sepharose matrix. Presumably, the polyoxosilicotungstates interact with positively charged domains on the viral envelope site(s) involved in the attachment of the (HCMV) virions to the cell surface receptor heparan sulphate.