Background
Zanamivir is a selective inhibitor of influenza A and B virus neuraminidases with IC50 values of 0.64-7.9nM [1].
Influenza A and B viruses are negative-strand RNA viruses. Neuraminidase is one of the two glycoproteins present on the surface of the virus. It is important to the pathogenicity and infectivity of the virus. The neuraminidases inhibitor, zanamivir, is a sialic acid analogue. It inhibits neuraminidases to cleave sialic acid on the surface of host cells and influenza viral envelope. In the in vitro assay, zanamivir suppresses the growth of influenza A and B viruses with IC50 values ranging from 5nM to 14nM for laboratory-passaged strains and from 20nM to 16μM for clinical isolates. In animal models infected with influenza A and B, treatment of zanamivir reduces the mortality and viral titres in lung homogenates and improves lung consolidation scores [1].
参考文献:
[1] Elliott M. Zanamivir: from drug design to the clinic. Philos Trans R Soc Lond B Biol Sci, 2001, 356(1416): 1885-93.
Protocol
| Cell experiment [1,2]: |
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Cell lines
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HeLa-CD4-LTR-βgal cells and HeLa-tat cell, CV-1 cell
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Preparation method
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The solubility of this compound in DMSO is >16.6mg/mL. General tips for obtaining a higher concentration: Please warm the tube at 37 ℃ for 10 minutes and/or shake it in the ultrasonic bath for a while. Stock solution can be stored below -20℃ for several months.
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Reacting condition
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5 nM-10 mM
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Applications
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In HeLa-CD4-LTR-βgal cells, zananivir interfered with cell-cell fusion with the IC50 of 0.19 mM. In CV-1 cell monolayers, zananivir (0.5 mM) reduced plaque area by 97%. Zananivir caused a concentration-dependent inhibition of hemadsorption. Zananivir (5 mM) strikingly reduced lipid mixing. zanamivir suppressed the growth of influenza A and B viruses with IC50 values of 5 nM-14 nM for laboratory-passaged strains and from 20 nM-16 μM for clinical isolates.
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| Animal experiment [2]: |
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Animal models
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Mice infected with influenza A
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Dosage form
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Intranasal, 0.01-4 mg/kg
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Application
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Intranasal zananivir treatment given prophylactically plus twice daily over days 0 to 3 in mice infected with influenza A reduced mortality and viral titres in lung homogenated and improved lung consolidation scores over 10 days.
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Other notes
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Please test the solubility of all compounds indoor, and the actual solubility may slightly differ with the theoretical value. This is caused by an experimental system error and it is normal.
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参考文献:
[1]. Greengard O, Poltoratskaia N, Leikina E, et al. The anti-influenza virus agent 4-GU-DANA (zanamivir) inhibits cell fusion mediated by human parainfluenza virus and influenza virus HA[J]. Journal of virology, 2000, 74(23): 11108-11114.
[2]. Elliott M. Zanamivir: from drug design to the clinic[J]. Philosophical Transactions of the Royal Society of London. Series B, 2001, 356(1416): 1885.
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