Therapeutic Targets Database
BIDD Pharmainformatics Databases
 
   
 

 

Target Validation Information
TTD IDTTDS00174
Target NameNeuraminidase    
Type of TargetSuccessful target    
Drug Potency against TargetZanamivirIC50 = 1.8 nM[1]
PeramivirIC50 = 1.8 nM[1]
KATSUMADAIN AIC50 = 1050 nM[2]
Cudratricusxanthone FIC50 = 1271 nM[3]
HERBACETINIC50 = 1400 nM[4]
MANGIFERINIC50 = 16200 nM[3]
APIGENINIC50 = 17400 nM[4]
Cudraxanthone MIC50 = 186 nM[3]
MACLURAXANTHONEIC50 = 186 nM[3]
Cudraxanthone LIC50 = 228 nM[3]
CUDRATRICUSXANTHONEIC50 = 245 nM[3]
Cudraxanthone DIC50 = 278 nM[3]
(S)-1,7-Diphenyl-6(E)-hepten-3-olIC50 = 4130 nM[2]
(E,E)-5-Hydroxy-1,7-diphenyl-4,6-heptadien-3-oneIC50 = 4670 nM[2]
(E,E)-1,7-Diphenyl-4,6-heptadien-3-oneIC50 = 6100 nM[2]
RHODIOLININIC50 = 6100 nM[4]
OSELTAMIVIR ACIDIC50 = 7.09 nM[5]
GOSSYPETINIC50 = 800 nM[4]
KAEMPFEROLIC50 = 8000 nM[4]
SMEATHXANTHONE AKi = 150 nM[6]
8-DEOXYGARTANINKi = 15500 nM[6]
GARCINONE DKi = 3300 nM[6]
GARTANINKi = 3600 nM[6]
MANGOSTINKi = 5800 nM[6]
MANGOSTANINKi = 5900 nM[6]
MANGOSTANOLKi = 6500 nM[6]
MANGOSTENONE GKi = 6800 nM[6]
MANGOSTENONE FKi = 7600 nM[6]
gamma-mangostinKi = 800 nM[6]
Action against Disease ModelZanamivirInfluenza virus neuraminidase inhibitors (NAIs) were introduced in clinical practice in various parts of the world since 1999 but were only scarcely distributed in France. Prior to 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 assay against 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.[7]
OseltamivirInfluenza virus neuraminidase inhibitors (NAIs) were introduced in clinical practice in various parts of the world since 1999 but were only scarcely distributed in France. Prior to 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 assay against 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.[7]
Ref 1Curr Top Med Chem. 2006;6(5):423-34.Optimization of small molecule drugs binding to highly polar target sites: lessons from the discovery and development of neuraminidase inhibitors. To Reference
Ref 2J Med Chem. 2010 Jan 28;53(2):778-86.Antiviral potential and molecular insight into neuraminidase inhibiting diarylheptanoids from Alpinia katsumadai. To Reference
Ref 3Bioorg Med Chem. 2009 Apr 1;17(7):2744-50. Epub 2009 Feb 26.Characteristic of neuraminidase inhibitory xanthones from Cudrania tricuspidata. To Reference
Ref 4Bioorg Med Chem. 2009 Oct 1;17(19):6816-23. Epub 2009 Aug 21.Neuraminidase inhibitory activities of flavonols isolated from Rhodiola rosea roots and their in vitro anti-influenza viral activities. To Reference
Ref 5Antimicrob Agents Chemother. 2008 Oct;52(10):3484-91. Epub 2008 Aug 11.Limited inhibitory effects of oseltamivir and zanamivir on human sialidases. To Reference
Ref 6Bioorg Med Chem. 2010 Sep 1;18(17):6258-64. Epub 2010 Jul 19.Xanthones with neuraminidase inhibitory activity from the seedcases of Garcinia mangostana. To Reference
Ref 7Antiviral Res. 2005 Oct;68(1):43-8.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. To Reference



 

Welcome to sign our Guestbook.

If you find any error in data or bug in web service, please kindly report it to Dr. Zhu.


Dr. Chen Yuzong
Deputy Director of Center for Computational Science and Engineering
Professor in Department of Pharmacy
National University of Singapore, Singapore


All rights reserved.

 
   
           
 
Computer-aided Drug Design
About BIDD | Databases | Software | Teaching | Research |  Links

Department of Computational Science | National University of Singapore | Blk S17, 3 Science Drive 2, Singapore 117543