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Showing drug card for Zanamivir (DB00558)

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Version 2.5
Creation Date 2005-06-13 13:24:05
Update Date 2009-06-23 18:05:58
Primary Accession Number DB00558
Secondary Accession Number
  • APRD00378
Name Zanamivir
Drug Type
  • Approved
  • Investigational
  • Small Molecule
Description A guanido-neuraminic acid that is used to inhibit neuraminidase. [PubChem]
Synonyms
  1. GANA
  2. GNA
  3. Modified sialic acid
  4. ZMR
  5. Zanamavir
Brand Names
  1. Relenza
Brand Mixtures Not Available
Chemical IUPAC Name (4S,5R,6R)-5-acetamido-4-(diaminomethylideneamino)-6-[(1R,2R)-1,2,3-trihydroxypropyl]-5,6-dihydro-4H-pyran-2-carboxylic acid
Chemical Formula C12H20N4O7
Chemical Structure Structure
CAS Registry Number 139110-80-8
InChI Identifier InChI=1/C12H20N4O7/c1-4(18)15-8-5(16-12(13)14)2-7(11(21)22)23-10(8)9(20)6(19)3-17/h2,5-6,8-10,17,19-20H,3H2,1H3,(H,15,18)(H,21,22)(H4,13,14,16)/t5-,6+,8+,9+,10+/m0/s1/f/h15,21H,13-14H2
InChI Key ARAIBEBZBOPLMB-OSZOJNELDI
KEGG Drug D00902 Link Image
KEGG Compound C08095 Link Image
PubChem Compound 60855 Link Image
PubChem Substance 197092 Link Image
ChEBI ID Not Available
PharmGKB ID PA451953 Link Image
HET ID ZMR Link Image
GenBank ID Not Available
Drug ID Number [DIN] 02240863 Link Image
RxList Link http://www.rxlist.com/cgi/generic2/zanam.htm Link Image
PDRhealth Link Not Available
Wikipedia Link http://en.wikipedia.org/wiki/Zanamivir Link Image
FDA Label
Material Safety Data Sheet (MSDS)
Synthesis Reference Not Available
Average Molecular Weight 332.3098
Monoisotopic Molecular Weight 332.1332
State Solid
Melting Point Not Available
Experimental Water Solubility 7.31 mg/mL [Predicted by ALOGPS] Source: PhysProp
Predicted Water Solubility 7.31e+00 mg/mL Calculated using ALOGPS
Experimental LogP/Hydrophobicity -3 Source: PhysProp
Predicted LogP -2.29 Calculated using ALOGPS
Experimental LogS Not Available
Predicted LogS -1.66 Calculated using ALOGPS
Experimental Caco2 Permeability Not Available
pKa/Isoelectric Point Not Available
Mass Spectrum Not Available
MOL File Show Link Image | Download Link Image
SDF File Show Link Image | Download Link Image
PDB File Show Link Image | Download Link Image
2D Structure
3D Structure
Experimental PDB ID 2BAT Link Image
Experimental PDB File Show
Experimental PDB Structure
Isomeric SMILES CC(=O)N[C@@H]1[C@H](C=C(O[C@H]1[C@H](O)[C@H](O)CO)C(O)=O)\N=C(/N)N
Canonical SMILES CC(=O)NC1C(C=C(OC1C(O)C(O)CO)C(O)=O)N=C(N)N
Drug Category
  • Antiviral Agents
  • Enzyme Inhibitors
  • Neuraminidase Inhibitors
ATC Codes
AHFS Codes
  • 08:18.28
Indication For the prevention and treatment of influenza.
Pharmacology Zanamivir, an antiviral agent, is a neuraminidase inhibitor indicated for treatment of uncomplicated acute illness due to influenza A and B virus in adults and pediatric patients 7 years and older who have been symptomatic for no more than 2 days. Zanamivir has also been shown to significantly inhibit the human sialidases NEU3 and NEU2 in the micromolar range (Ki 3.7 +/-0.48 and 12.9+/-0.07 microM, respectively), which could account for some of the rare side effects of zanamivir.
Mechanism of Action The proposed mechanism of action of zanamivir is via inhibition of influenza virus neuraminidase with the possibility of alteration of virus particle aggregation and release.
Absorption Absolute bioavailability is very low following oral administration (2%). Following oral inhalation, bioavailability is 4% to 17%.
Toxicity Not Available
Protein Binding Zanamivir has limited plasma protein binding (<10%).
Biotransformation Not metabolized
Half Life 2.5-5.1 hours
Dosage Forms
Form Route
Powder Respiratory (inhalation)
Patient Information Show Link Image
Contraindications Show Link Image
Interactions Show Link Image
Drug Interactions Not Available
Food Interactions Not Available
Pathways Not Available
General References
  1. Sugaya N, Tamura D, Yamazaki M, Ichikawa M, Kawakami C, Kawaoka Y, Mitamura K: Comparison of the clinical effectiveness of oseltamivir and zanamivir against influenza virus infection in children. Clin Infect Dis. 2008 Aug 1;47(3):339-45. [PubMed Link Image]
  2. Hata K, Koseki K, Yamaguchi K, Moriya S, Suzuki Y, Yingsakmongkon S, Hirai G, Sodeoka M, von Itzstein M, Miyagi T: Limited Inhibitory Effects of Oseltamivir and Zanamivir on Human Sialidases. Antimicrob Agents Chemother. 2008 Aug 11. [PubMed Link Image]
  3. Meindl P, Bodo G, Palese P, Schulman J, Tuppy H: Inhibition of neuraminidase activity by derivatives of 2-deoxy-2,3-dehydro-N-acetylneuraminic acid. Virology. 1974 Apr;58(2):457-63. [PubMed Link Image]
  4. von Itzstein M, Wu WY, Kok GB, Pegg MS, Dyason JC, Jin B, Van Phan T, Smythe ML, White HF, Oliver SW, et al.: Rational design of potent sialidase-based inhibitors of influenza virus replication. Nature. 1993 Jun 3;363(6428):418-23. [PubMed Link Image]
  5. Drugs.com Link Image
  6. Wikipedia Link Image
  7. RxList Link Image
Organisms Affected
  • Influenza A virus
  • Influenza B virus
Targets
  1. Neuraminidase
  2. Neuraminidase
Drug Target 1 [top]
Target 1 ID 64
Target 1 Name Neuraminidase
Target 1 Synonyms
  1. EC 3.2.1.18
Target 1 Gene Name NA
Target 1 Protein Sequence >Neuraminidase 
MNPNQKIITIGSVSLTIATICFLMQIAILVTTVTLHFKQYECSSPPNNQVMPCEPIIIER
NITEIVYLTNTTIDKEICPKLVEYRNWSKPQCKITGFAPFSKDNSIRLSAGGGIWVTREP
YVSCDPGKCYQFALGQGTTLDNKHSNDTIHDRTPYRTLLMNELGVPFHLGTRQVCIAWSS
SSCHDGKAWLHVCVTGYDKNATASFIYDGRLVDSIGSWSKNILRTQESECVCINGTCTVV
MTDGSASERADTKILFIEEGKIVHISPLSGSAQHVEECSCYPRYPGVRCVCRDNWKGSNR
PVVDINVKDYSIVSSYVCSGLVGDTPRKNDRSSSSYCRNPNNEKGNHGVKGWAFDDGNDV
WMGRTISEESRSGYETFKVIGGWSTPNSKLQINRQVIVDSDNRSGYSGIFSVEGKSCINR
CFYVELIRGREQETRVWWTSNSIVVFCGTSGTYGTGSWPDGADINLMPI
Target 1 Number of Residues 476
Target 1 Molecular Weight 52141
Target 1 Theoretical pI 7.28
Target 1 GO Classification
Function
catalytic activity
hydrolase activity
hydrolase activity, acting on glycosyl bonds
hydrolase activity, hydrolyzing O-glycosyl compounds
alpha-sialidase activity
exo-alpha-sialidase activity
Process
physiological process
metabolism
macromolecule metabolism
carbohydrate metabolism
Component
cell
membrane
Target 1 General Function Involved in exo-alpha-sialidase activity
Target 1 Specific Function Catalyzes the removal of terminal sialic acid residues from viral and cellular glycoconjugates. Cleaves off the terminal sialic acids on the glycosylated HA during virus budding to facilitate virus release. Additionally helps virus spread through the circulation by further removing sialic acids from the cell surface. These cleavages prevent self-aggregation and ensure the efficient spread of the progeny virus from cell to cell. Otherwise, infection would be limited to one round of replication. Described as a receptor-destroying enzyme because it cleaves a terminal sialic acid from the cellular receptors. May facilitate viral invasion of the upper airways by cleaving the sialic acid moities on the mucin of the airway epithelial cells. Likely to plays a role in the budding process through its association with lipid rafts during intracellular transport. May additionally display a raft-association independent effect on budding. Plays a role in the determination of host range restriction on replication and virulence. Sialidase activity in late endosome/lysosome traffic seems to enhance virus replication
Target 1 Pathways
Name SMPDB Link KEGG Link
Glycosphingolipid metabolism map00600 Link Image
N-Glycan degradation map00511 Link Image
Target 1 Reactions
  • Hydrolysis of alpha-(2->3)-, alpha-(2->6)-, alpha-(2->8)- glycosidic linkages of terminal sialic acid residues in oligosaccharides, glycoproteins, glycolipids, colominic acid and synthetic substrates ALL_REAC (other) R03491 R04018 R04634 R04650 R05115 R05117 R05996(G) R05998(G) R05999(G) R06012(G) R06147(G) R06253(G) INHIBITOR 2-Deoxy-2,3-dehydro-N-acetylneuraminic acid
Target 1 Pfam Domain Function
Target 1 Signals
  • None
Target 1 Transmembrane Regions
  • 7-35
Target 1 Essentiality Essential
Target 1 GenBank ID Protein 324460 Link Image
Target 1 UniProtKB/Swiss-Prot ID P06818 Link Image
Target 1 UniProtKB/Swiss-Prot Entry Name NRAM_IABAN Link Image
Target 1 PDB ID 2BAT Link Image
Target 1 PDB File Show
Target 1 3D Structure
Target 1 Cellular Location
  • Virion
  • apical cell membrane
  • single-pass type II membrane protein (
  • virion membrane. Cell membrane
Target 1 Gene Sequence >1410 bp 
ATGAATCCAAATCAAAAGATAATAACAATTGGCTCTGTCTCTCTCACCATTGCAACAATA
TGCTTCCTTATGCAAATTGCCATCCTGGTAACTACTGTAACATTGCATTTCAAGCAATAT
GAGTGCAGCTCCCCCCCAAACAACCAAGTAATGCCGTGTGAACCAATAATAATAGAAAGA
AACATAACAGAGATAGTGTATTTGACTAACACCACCATAGACAAAGAGATATGCCCCAAA
TTAGTGGAATACAGAAATTGGTCAAAGCCGCAATGTAAAATTACAGGATTTGCACCTTTT
TCTAAGGACAATTCAATTCGGCTTTCTGCTGGTGGGGGCATTTGGGTGACGAGAGAACCT
TATGTGTCATGCGATCCTGGCAAGTGTTATCAATTTGCACTCGGGCAGGGGACCACACTA
GACAACAAGCATTCAAATGACACAATACATGATAGGACCCCTTATCGAACCCTATTGATG
AATGAGTTGGGTGTTCCATTTCATTTGGGAACCAGGCAAGTGTGTATAGCATGGTCCAGC
TCAAGTTGTCACGATGGAAAAGCATGGCTGCATGTTTGTGTCACTGGGTATGATAAAAAT
GCAACTGCTAGCTTCATTTACGATGGGAGGCTTGTAGACAGTATTGGTTCATGGTCCAAA
AATATCCTCAGGACCCAGGAGTCGGAATGCGTTTGTATCAATGGGACTTGTACAGTAGTA
ATGACTGATGGAAGTGCTTCAGAAAGAGCTGATACTAAAATACTATTCATTGAAGAGGGG
AAAATCGTTCATATTAGCCCATTGTCAGGAAGTGCTCAGCATGTAGAGGAGTGTTCCTGT
TATCCTCGATATCCTGGTGTCAGATGTGTCTGCAGAGACAACTGGAAAGGCTCCAATAGG
CCCGTCGTAGATATAAATGTGAAAGATTATAGCATTGTTTCCAGTTATGTGTGCTCAGGG
CTTGTTGGCGACACACCCAGAAAAAACGACAGATCTAGCAGTAGCTATTGCCGGAATCCT
AACAATGAGAAAGGGAATCATGGAGTGAAAGGCTGGGCCTTTGACGATGGAAATGACGTG
TGGATGGGAAGAACGATCAGCGAGGAGTCACGATCAGGTTATGAAACCTTCAAAGTCATT
GGTGGTTGGTCCACACCTAATTCCAAATTGCAGATAAATAGGCAAGTCATAGTTGACAGC
GATAATAGGTCCGGTTATTCTGGTATTTTCTCTGTTGAGGGCAAAAGCTGCATCAATAGG
TGCTTTTATGTGGAGTTGATAAGGGGAAGGGAACAGGAAACTAGAGTCTGGTGGACCTCA
AACAGTATTGTTGTGTTTTGTGGCACTTCAGGTACCTATGGAACAGGCTCATGGCCTGAT
GGAGCGGACATCAATCTCATGCCTATATAA
Target 1 GenBank Gene ID
Target 1 GeneCard ID Not Available
Target 1 GenAtlas ID Not Available
Target 1 HGNC ID Not Available
Target 1 Chromosome Location Not Available
Target 1 Locus Not Available
Target 1 SNPs SNPJam Report Link Image
Target 1 General References
  1. Martinez C, del Rio L, Portela A, Domingo E, Ortin J: Evolution of the influenza virus neuraminidase gene during drift of the N2 subtype. Virology. 1983 Oct 30;130(2):539-45. [PubMed Link Image]
Target 1 Drug References
  1. Murrell MT, Porotto M, Greengard O, Poltoratskaia N, Moscona A: A single amino acid alteration in the human parainfluenza virus type 3 hemagglutinin-neuraminidase glycoprotein confers resistance to the inhibitory effects of zanamivir on receptor binding and neuraminidase activity. J Virol. 2001 Jul;75(14):6310-20. [PubMed Link Image]
  2. Mungall BA, Xu X, Klimov A: Assaying susceptibility of avian and other influenza A viruses to zanamivir: comparison of fluorescent and chemiluminescent neuraminidase assays. Avian Dis. 2003;47(3 Suppl):1141-4. [PubMed Link Image]
  3. Macdonald SJ, Cameron R, Demaine DA, Fenton RJ, Foster G, Gower D, Hamblin JN, Hamilton S, Hart GJ, Hill AP, Inglis GG, Jin B, Jones HT, McConnell DB, McKimm-Breschkin J, Mills G, Nguyen V, Owens IJ, Parry N, Shanahan SE, Smith D, Watson KG, Wu WY, Tucker SP: Dimeric zanamivir conjugates with various linking groups are potent, long-lasting inhibitors of influenza neuraminidase including H5N1 avian influenza. J Med Chem. 2005 Apr 21;48(8):2964-71. [PubMed Link Image]
Drug Target 2 [top]
Target 2 ID 6007
Target 2 Name Neuraminidase
Target 2 Synonyms
  1. EC 3.2.1.18
Target 2 Gene Name NA
Target 2 Protein Sequence >Neuraminidase 
MLPSTIQTLTLFLTSGGVLLSLYVSASLSYLLYSDILLKFSSKITAPTMTLDCANASNVQ
AVNRSATKEMTFLLPEPEWTYPRLSCQGSTFQKALLISPHRFGEARGNSAPLIIREPFIA
CGPKECKHFALTHYAAQPGGYYNGTREDRNKLRHLISVKLGKIPTVENSIFHMAAWSGSA
CHDGREWTYIGVDGPDSNALIKIKYGEAYTDTYHSYANNILRTQESACNCIGGDCYLMIT
DGSASGISKCRFLKIREGRIIKEIFPTGRVEHTEECTCGFASNKTIECACRDNSYTAKRP
FVKLNVETDTAEIRLMCTETYLDTPRPDDGSITGPCESNGDKGRGGIKGGFVHQRMASKI
GRWYSRTMSKTERMGMELYVRYDGDPWTDSDALAHSGVMVSMKEPGWYSFGFEIKDKKCD
VPCIGIEMVHDGGKKTWHSAATAIYCLMGSGQLLWDTVTGVDMAL
Target 2 Number of Residues 472
Target 2 Molecular Weight 51430
Target 2 Theoretical pI 7.55
Target 2 GO Classification
Function
catalytic activity
hydrolase activity
hydrolase activity, acting on glycosyl bonds
hydrolase activity, hydrolyzing O-glycosyl compounds
alpha-sialidase activity
exo-alpha-sialidase activity
Process
physiological process
metabolism
macromolecule metabolism
carbohydrate metabolism
Component
cell
membrane
Target 2 General Function Not Available
Target 2 Specific Function Catalyzes the removal of terminal sialic acid residues from viral and cellular glycoconjugates. Cleaves off the terminal sialic acids on the glycosylated HA during virus budding to facilitate virus release. Additionally helps virus spread through the circulation by further removing sialic acids from the cell surface. These cleavages prevent self-aggregation and ensure the efficient spread of the progeny virus from cell to cell. Otherwise, infection would be limited to one round of replication. Described as a receptor-destroying enzyme because it cleaves a terminal sialic acid from the cellular receptors. May facilitate viral invasion of the upper airways by cleaving the sialic acid moities on the mucin of the airway epithelial cells (By similarity)
Target 2 Pathways Not Available
Target 2 Reactions Not Available
Target 2 Pfam Domain Function
Target 2 Signals
  • None
Target 2 Transmembrane Regions
  • 7-35
Target 2 Essentiality Essential
Target 2 GenBank ID Protein Not Available
Target 2 UniProtKB/Swiss-Prot ID P27907 Link Image
Target 2 UniProtKB/Swiss-Prot Entry Name NRAM_INBBE Link Image
Target 2 PDB ID 1A4Q Link Image
Target 2 PDB File Show
Target 2 3D Structure
Target 2 Cellular Location
  • Virion membrane (By similarity). Apical cell membrane
Target 2 Gene Sequence Not Available
Target 2 GenBank Gene ID
Target 2 GeneCard ID Not Available
Target 2 GenAtlas ID Not Available
Target 2 HGNC ID Not Available
Target 2 Chromosome Location Not Available
Target 2 Locus Not Available
Target 2 SNPs SNPJam Report Link Image
Target 2 General References
  1. Burmeister WP, Ruigrok RW, Cusack S: The 2.2 A resolution crystal structure of influenza B neuraminidase and its complex with sialic acid. EMBO J. 1992 Jan;11(1):49-56. [PubMed Link Image]
  2. Burmeister WP, Daniels RS, Dayan S, Gagnon J, Cusack S, Ruigrok RW: Sequence and crystallization of influenza virus B/Beijing/1/87 neuraminidase. Virology. 1991 Jan;180(1):266-72. [PubMed Link Image]
  3. Taylor NR, Cleasby A, Singh O, Skarzynski T, Wonacott AJ, Smith PW, Sollis SL, Howes PD, Cherry PC, Bethell R, Colman P, Varghese J: Dihydropyrancarboxamides related to zanamivir: a new series of inhibitors of influenza virus sialidases. 2. Crystallographic and molecular modeling study of complexes of 4-amino-4H-pyran-6-carboxamides and sialidase from influenza virus types A and B. J Med Chem. 1998 Mar 12;41(6):798-807. [PubMed Link Image]
Target 2 Drug References
  1. Eiland LS, Eiland EH: Zanamivir for the prevention of influenza in adults and children age 5 years and older. Ther Clin Risk Manag. 2007 Jun;3(3):461-5. [PubMed Link Image]

This project is supported by Genome Alberta & Genome Canada, a not-for-profit organization that is leading Canada's national genomics strategy with $600 million in funding from the federal government. This project is also supported in part by GenomeQuest, Inc., an enterprise genomic information company serving the life science community.