A Small-Molecule Inhibitor of Nipah Virus Envelope Protein-Mediated Membrane Fusion

作者：Niedermeier Sabine; Singethan Katrin; Rohrer Sebastian G; Matz Magnus; Kossner Markus; Diederich Sandra; Maisner Andrea; Schmitz Jens; Hiltensperger Georg; Baumann Knut; Holzgrabe Ulrike^*; Schneider Schaulies Jurgen

来源：Journal of Medicinal Chemistry, 2009, 52(14): 4257-4265.

DOI：10.1021/jm900411s

Nipah virus (NiV), a highly pathogenic paramyxovirus. causes respiratory disease in pigs and severe febrile encephalitis in humans with high mortality rates. On the basis of the structural similarity of viral fusion (F) proteins within the family Paramyxoviridae, we designed and tested 18 quinolone derivatives in a NiV and measles virus (MV) envelope protein-based fusion assay beside evaluation of cytotoxicity. We found five compounds successfully inhibiting NiV envelope protein-induced cell fusion. The most active molecules (19 and 20), which also inhibit the syncytium formation induced by infectious NiV and show a low cytotoxicity in Vero cells, represent a promising lead quinolone-type compound structure. Molecular modeling indicated that compound 19 fits well into a particular protein cavity present on the NiV F protein that is important for the fusion process.

• 出版日期2009-7-23