A small-molecule inhibitor of Nipah virus envelope protein-mediated membrane fusion.
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.
Niedermeier
Sabine
S
Institute of Pharmacy and Food Chemistry, University of Würzburg, Am Hubland, 97080 Würzburg, Germany.
Singethan
Katrin
K
Rohrer
Sebastian G
SG
Matz
Magnus
M
Kossner
Markus
M
Diederich
Sandra
S
Maisner
Andrea
A
Schmitz
Jens
J
Hiltensperger
Georg
G
Baumann
Knut
K
Holzgrabe
Ulrike
U
Schneider-Schaulies
Jürgen
J
D000818:Animals; D002460:Cell Line; D002522:Chlorocebus aethiops; D003198:Computer Simulation; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D006801:Humans; D008459:Measles virus / Q000187:drug effects / Q000378:metabolism / Q000502:physiology; D008958:Models, Molecular; D008968:Molecular Conformation; D045405:Nipah Virus / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D015363:Quinolones / Q000737:chemistry / Q000494:pharmacology; D014759:Viral Envelope Proteins / Q000737:chemistry / Q000378:metabolism*; D053586:Virus Internalization / Q000187:drug effects*
D015363:Quinolones; D014759:Viral Envelope Proteins