Target Validation Information
TTD ID T31595
Target Name Influenza Neuraminidase (Influ NA)
Type of Target
Successful
Drug Potency against Target Zanamivir Drug Info IC50 = 1.8 nM [6]
Peramivir Drug Info IC50 = 1.8 nM [6]
(E,E)-1,7-Diphenyl-4,6-heptadien-3-one Drug Info IC50 = 6100 nM [3]
(E,E)-5-Hydroxy-1,7-diphenyl-4,6-heptadien-3-one Drug Info IC50 = 4670 nM [3]
(S)-1,7-Diphenyl-6(E)-hepten-3-ol Drug Info IC50 = 4130 nM [3]
8-DEOXYGARTANIN Drug Info Ki = 15500 nM [4]
APIGENIN Drug Info IC50 = 17400 nM [2]
CUDRATRICUSXANTHONE Drug Info IC50 = 245 nM [1]
Cudraxanthone D Drug Info IC50 = 278 nM [1]
Cudraxanthone L Drug Info IC50 = 228 nM [1]
Cudraxanthone M Drug Info IC50 = 186 nM [1]
Gamma-mangostin Drug Info Ki = 800 nM [4]
GARCINONE D Drug Info Ki = 3300 nM [4]
GARTANIN Drug Info Ki = 3600 nM [4]
GOSSYPETIN Drug Info IC50 = 800 nM [2]
HERBACETIN Drug Info IC50 = 1400 nM [2]
KAEMPFEROL Drug Info IC50 = 8000 nM [2]
KATSUMADAIN A Drug Info IC50 = 1050 nM [3]
MACLURAXANTHONE Drug Info IC50 = 186 nM [1]
MANGIFERIN Drug Info IC50 = 16200 nM [1]
MANGOSTANIN Drug Info Ki = 5900 nM [4]
MANGOSTANOL Drug Info Ki = 6500 nM [4]
MANGOSTENONE F Drug Info Ki = 7600 nM [4]
MANGOSTENONE G Drug Info Ki = 6800 nM [4]
MANGOSTIN Drug Info Ki = 5800 nM [4]
RHODIOLININ Drug Info IC50 = 6100 nM [2]
SMEATHXANTHONE A Drug Info Ki = 150 nM [4]
Action against Disease Model Oseltamivir Drug Info Influenza virus neuraminidase inhibitors (NAIs) were introduced in clinical practice in various parts of the world since 1999 but were only scarcely distributed in France. Priorto the generalization of zanamivir and oseltamivir utilization in our country, we decided to test a large panel of influenza strains to establish the baseline sensitivity of these viruses to anti-neuraminidase drugs, based upon a fluorometric neuraminidase enzymatic test. Our study was performed on clinical samples collected by practitioners of the GROG network (Groupe R?|gional d'Observation de la Grippe) in the south of France during the 2002-2003 influenza season. Out of 355 isolates tested in the fluorometric neuraminidase activity assay, 267 isolates could be included in inhibition assayagainst anti-neuraminidase drugs. Differences in IC50 range were found according to the subtype and the anti-neuraminidase drug. Influenza B and A/H1N1 viruses appeared to be more sensitive to zanamivir than to oseltamivir (mean B IC50 values: 4.19 nM versus 13 nM; mean H1N1 IC50 values: 0.92 nM versus 1.34 nM), while A/H1N2 and A/H3N2 viruses were more sensitive to oseltamivir than to zanamivir (mean H3N2 IC50 values: 0.67 nM versus 2.28 nM; mean H1N2 IC50 values: 0.9 nM versus 3.09 nM). Out of 128 N2 carrying isolates, 10 isolates had zanamivir or oseltamivir IC50 values in upper limits compared to their respective data range. Sequencing of the neuraminidase of these outliers N2 highlighted several mutations, but none of them were associated with resistance to neuraminidase inhibitors. [5]
Zanamivir Drug Info Influenza virus neuraminidase inhibitors (NAIs) were introduced in clinical practice in various parts of the world since 1999 but were only scarcely distributed in France. Priorto the generalization of zanamivir and oseltamivir utilization in our country, we decided to test a large panel of influenza strains to establish the baseline sensitivity of these viruses to anti-neuraminidase drugs, based upon a fluorometric neuraminidase enzymatic test. Our study was performed on clinical samples collected by practitioners of the GROG network (Groupe R?|gional d'Observation de la Grippe) in the south of France during the 2002-2003 influenza season. Out of 355 isolates tested in the fluorometric neuraminidase activity assay, 267 isolates could be included in inhibition assayagainst anti-neuraminidase drugs. Differences in IC50 range were found according to the subtype and the anti-neuraminidase drug. Influenza B and A/H1N1 viruses appeared to be more sensitive to zanamivir than to oseltamivir (mean B IC50 values: 4.19 nM versus 13 nM; mean H1N1 IC50 values: 0.92 nM versus 1.34 nM), while A/H1N2 and A/H3N2 viruses were more sensitive to oseltamivir than to zanamivir (mean H3N2 IC50 values: 0.67 nM versus 2.28 nM; mean H1N2 IC50 values: 0.9 nM versus 3.09 nM). Out of 128 N2 carrying isolates, 10 isolates had zanamivir or oseltamivir IC50 values in upper limits compared to their respective data range. Sequencing of the neuraminidase of these outliers N2 highlighted several mutations, but none of them were associated with resistance to neuraminidase inhibitors. [5]
References
REF 1 Characteristic of neuraminidase inhibitory xanthones from Cudrania tricuspidata. Bioorg Med Chem. 2009 Apr 1;17(7):2744-50.
REF 2 Neuraminidase inhibitory activities of flavonols isolated from Rhodiola rosea roots and their in vitro anti-influenza viral activities. Bioorg Med Chem. 2009 Oct 1;17(19):6816-23.
REF 3 Antiviral potential and molecular insight into neuraminidase inhibiting diarylheptanoids from Alpinia katsumadai. J Med Chem. 2010 Jan 28;53(2):778-86.
REF 4 Xanthones with neuraminidase inhibitory activity from the seedcases of Garcinia mangostana. Bioorg Med Chem. 2010 Sep 1;18(17):6258-64.
REF 5 Sensitivity of influenza viruses to zanamivir and oseltamivir: a study performed on viruses circulating in France prior to the introduction of neuraminidase inhibitors in clinical practice. Antiviral Res. 2005 Oct;68(1):43-8.
REF 6 Optimization of small molecule drugs binding to highly polar target sites: lessons from the discovery and development of neuraminidase inhibitors. Curr Top Med Chem. 2006;6(5):423-34.

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