| 摘要 |
<p>New use of at least one active agent (I) (preferably a combination of two agents) for the prophylaxis and/or therapy of viral diseases. (I) either: (a) acts on at least two kinases of a signal transduction pathway to inhibit viral replication; or (b) inhibits SEK kinase. Independent claims are also included for: (i) combination preparations containing at least two of the active agents (I), as a mixture or as a individual components for simultaneous or successive use (by the same route or different routes); (ii) test systems for screening active agents for activity as for (I), comprising at least one type of infectable cells containing the signal transduction pathway kinases or SEK-kinase(s) as described for (I) and at least one virus for infecting the cells (or the cells already infected with the virus); (iii) a screening method corresponding to (ii), comprising contacting test compounds with the test system as in (ii) and detecting the effect on viral multiplication; and (iv) a method for preparing a medicament for the prophylaxis and/or therapy of viral diseases, comprising screening test compounds using the test system as in (ii) and formulating active compound(s) identified by the method with one or more auxiliaries and/or additives. ACTIVITY : Virucide. Permissive MDCK cells were infected at a multiplicity of infection of 0.01 with influenza-A viruses (A/FPV/Bratislava (H7N7) and A/WSN-HK (H3N1)) and influenza-B virus/Massachusetts, then treated with: (a) the kinase inhibitor U0126 (Ia) at the optimal antiviral concentration (see Nature Cell Biol. 3, 301-305, 2001), (b) amantadine (Ib) (a non-kinase inhibiting antiviral at the optimal antiviral concentration (see EMBOJ 11, 3021-3024, 1985) or (c) combinations of (Ia) and (Ib). 48 Hours after infection the titers of infectious virus particles in the cell culture supernatants were determined. The cell supernatants were diluted and used to infect fresh cells, then the infection cycle was repeated twice more. Results showed that the combination of (Ia) and (Ib) had synergistic action in inhibiting viral replication. MECHANISM OF ACTION : Cellular Signal Transduction Pathway Kinase Modulator; SEK Kinase Inhibitor.</p> |
