ro-09-0410 and disoxaril

Topics: Animals; Anti-Infective Agents; Antiviral Agents; Chalcone; Chalcones; Ciprofloxacin; Flavonoids; Fluoroquinolones; Furans; Humans; Isoxazoles; Ketones; Picornaviridae; Picornaviridae Infections; Quinolines; Rhinovirus; Structure-Activity Relationship

The effect of four structurally diverse capsid-binding compounds on the adsorption of seven human rhinoviruses (HRV), representative for both receptor and antiviral groupings was studied using infective center assays. Antiviral compounds studied included a pyridazinamine (R 61837), an isoxazole (WIN 51711), a flavan (4',6-dichloroflavan) and a chalcone (Ro-09410). Minor receptor viruses studied were HRV 1A, HRV 2 and HRV 29 (antiviral group B), major receptor viruses were HRV 9, HRV 39 and HRV 14, HRV 35 (antiviral group B and A, respectively). The adsorption of four out of the seven serotypes was inhibited by some antiviral compounds, but not by others, indicating that the conformational alterations induced by antiviral compounds can vary considerably within a given serotype, depending on the chemical nature of the antiviral compound used. A correlation between inhibition of adsorption and receptor grouping or antiviral grouping could not be found.

Topics: Adsorption; Antiviral Agents; Capsid; Chalcone; Chalcones; Flavonoids; HeLa Cells; Humans; Isoxazoles; Mutation; Protein Conformation; Pyridazines; Receptors, Virus; Rhinovirus

The entry of animal viruses into cells is associated with permeabilization of the infected cells to protein toxins such as alpha-sarcin (C. Fernández-Puentes and L. Carrasco, Cell 20:769-775, 1980). This phenomenon has been referred to as "the early permeabilization by animal viruses" (L. Carrasco, Virology 113:623-629, 1981). A number of inhibitors of poliovirus growth such as WIN 51711 6-(3,4-dichlorophenoxy)-3-(ethylthio)-2-pyridincarbonitrile (DEPC) and Ro 09-0410 specifically block the uncoating step of poliovirus but have no effect on attachment or entry of poliovirus particles into cells. These agents are potent inhibitors of the early permeabilization induced by poliovirus to the toxin alpha-sarcin. Thus, the uncoating of poliovirus is required for the permeabilization of cell membranes to proteins. The increased entry of labeled heparin promoted by virus entry is not blocked by these agents, indicating that poliovirus binds to its receptor and is internalized along with heparin in endosomes in the presence of WIN 51711, DEPC, or Ro 09-0410. We conclude that the delivery to the cytoplasm of some molecules that coenter with virion particles does not take place if the uncoating process is hindered.

Topics: Antiviral Agents; Cell Membrane; Cell Membrane Permeability; Cells, Cultured; Chalcone; Chalcones; Endoribonucleases; Fungal Proteins; HeLa Cells; Heparin; Humans; Isoxazoles; Phosphatidylcholines; Poliovirus; Protein Synthesis Inhibitors; Virion