A cell-permeable isoxazolylpiperazine compound that is shown to inhibit influenza A H1N1 (A/WSN/33 strain), H3N2 (clinical isolate), and H5N1 (A/Vietnam/1194/04) replication in MDCK cells.
A cell-permeable isoxazolylpiperazine compound that is shown to inhibit influenza A H1N1 (A/WSN/33 strain), H3N2 (clinical isolate), and H5N1 (A/Vietnam/1194/04) replication in MDCK cells in vitro (EC50 = 69, 160, and 330 nM, respectively) and significantly reduce fatality after A/Vietnam/1194/04 infection in mice in vivo (50% survial rate on day 21 with 14 b.i.d. i.p. doses of 230 µg/mouse in the first 7 days after infection) by preventing nucleoprotein (NP) nuclear accumulation via NP aggregation induction during early stages of viral infection. Virus strains with N309K or Y289H NP mutation, such as swine-origin influenza A (S-OIV) H1N1, are found to be resistant to Nucleozin, consistent with the N309-mediated hydrogen bonding and Y289-mediated hydrophobic interaction with Nucleozin as predicted by computer-aided docking studies.
Warning
Toxicity: Standard Handling (A)
Other Notes
Kao, R.Y., et al. 2010. Nat. Biotechnol.28, 600.
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CALBIOCHEM is a registered trademark of Merck KGaA, Darmstadt, Germany
Storage Class
11 - Combustible Solids
wgk_germany
WGK 3
flash_point_f
Not applicable
flash_point_c
Not applicable
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Negative-sense RNA viruses (NSVs) rely on prepackaged viral RNA-dependent RNA polymerases (RdRp) to replicate and transcribe their viral genomes. Their replication machinery consists of an RdRp bound to viral RNA which is wound around a nucleoprotein (NP) scaffold, forming a
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