N-(3-Cyanophenyl)-2-phenylacetamide, an effective inhibitor of morbillivirus-induced membrane fusion with low cytotoxicity

Based on the structural similarity of viral fusion proteins within the family Paramyxoviridae, we tested recently described and newly synthesized acetanilide derivatives for their capacity to inhibit measles virus (MV)-, canine distemper virus (CDV)- and Nipah virus (NiV)-induced membrane fusion. We found that N-(3-cyanophenyl)-2-phenylacetamide (compound 1) has a high capacity to inhibit MV- and CDV-induced (IC(50) muM), but not NiV-induced, membrane fusion. This compound is of outstanding interest because it can be easily synthesized and its cytotoxicity is low [50 % cytotoxic concentration (CC(50)) >/= 300 muM], leading to a CC(50)/IC(50) ratio of approximately 100. In addition, primary human peripheral blood lymphocytes and primary dog brain cell cultures (DBC) also tolerate high concentrations of compound 1. Infection of human PBMC with recombinant wild-type MV is inhibited by an IC(50) of approximately 20 muM. The cell-to-cell spread of recombinant wild-type CDV in persistently infected DBC can be nearly completely inhibited by compound 1 at 50 muM, indicating that the virus spread between brain cells is dependent on the activity of the viral fusion protein. Our findings demonstrate that this compound is a most applicable inhibitor of morbillivirus-induced membrane fusion in tissue culture experiments including highly sensitive primary cells.

Der Übergang ins Hochschulstudium: Prozesse und Mechanismen am Beispiel der deutschen Schweiz

Im Allgemeinen wird zum einen die Auffassung geteilt, dass auch ein Land wie die Schweiz auf ein steigendes Angebot qualifizierter und hochqualifizierter Arbeitskräfte angewiesen ist, um wirtschaftliche Prosperität und allgemeine Wohlfahrt dauerhaft sicherstellen zu können (vgl. SKBF 2010). Zum anderen wird dem modernen Bildungssystem – unter Gewährleistung zumindest formaler Chancengleichheit – die Aufgabe zugeschrieben, mittels ausreichender Bildungsgelegenheiten für dieses Angebot an Humankapital zu sorgen (vgl. Müller und Kogan 2010; Müller et al. 1997; Seibert et al. 2010).