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Identification
Name Zanamivir
Accession Number DB00558 (APRD00378)
Type small molecule
Groups approved
Description

A guanido-neuraminic acid that is used to inhibit neuraminidase. [PubChem]
Structure Thumb
Download: MOL | SDF | SMILES | InChI
Display: 2D Structure | 3D Structure
Synonyms
GANA
GNA
Modified sialic acid
Zanamavir
ZMR
Salts Not Available
Brand names
Name Company
Relenza GlaxoSmithKline
Brand mixtures Not Available
Categories
  • Antiviral Agents
  • Enzyme Inhibitors
  • Neuraminidase Inhibitors
CAS number 139110-80-8
Weight Average: 332.3098
Monoisotopic: 332.133199014
Chemical Formula C12H20N4O7
InChI Key InChIKey=ARAIBEBZBOPLMB-UFGQHTETSA-N
InChI
InChI=1S/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
Plain Text
IUPAC Name
(2R,3R,4S)-4-[(diaminomethylidene)amino]-3-acetamido-2-[(1R,2R)-1,2,3-trihydroxypropyl]-3,4-dihydro-2H-pyran-6-carboxylic acid
SMILES
[H][C@]1(OC(=C[C@H](N=C(N)N)[C@H]1NC(C)=O)C(O)=O)[C@H](O)[C@H](O)CO
Plain Text
Mass Spec Not Available
Taxonomy
Kingdom Organic
Classes
  • Glycerol and Derivatives
  • Pyrans
  • Ethers
  • Carboxylic Acids and Derivatives
Substructures
  • Glycerol and Derivatives
  • Hydroxy Compounds
  • Pyrans
  • Acetates
  • Amino Ketones
  • Ethers
  • Carboxylic Acids and Derivatives
  • Alcohols and Polyols
  • Heterocyclic compounds
  • Guanidines
  • Carboxamidines
  • Carboxamides and Derivatives
Pharmacology
Indication For the prevention and treatment of influenza A and B.
Pharmacodynamics 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. By binding and inhibiting the neuraminidase protein, the drug renders the influenza virus unable to escape its host cell and infect others.
Absorption Absolute bioavailability is very low following oral administration (2%). Following oral inhalation, bioavailability is 4% to 17%.
Volume of distribution Not Available
Protein binding Zanamivir has limited plasma protein binding (<10%).
Metabolism Not metabolized
Route of elimination It is excreted unchanged in the urine with excretion of a single dose completed within 24 hours. Unabsorbed drug is excreted in the feces.Zanamivir is renally excreted as unchanged drug.
Half life 2.5-5.1 hours
Clearance
  • 2.5 – 10.9 L/h [Following oral inhalation 10 mg]
  • 5.3 L/h [Normal renal function receiving IV single dose of 4 mg or 2 mg]
  • 2.7 L/h [Patients with mild and moderate renal impairement receiving IV single dose of 4 mg or 2 mg]
  • 0.8 L/h [Patients with severe renal impairement receiving IV single dose of 4 mg or 2 mg]
Toxicity Not Available
Affected organisms
  • Influenza A virus
  • Influenza B virus
Pathways Not Available
Pharmacoeconomics
Manufacturers
  • Glaxosmithkline
Packagers
Dosage forms
Form Route Strength
Powder Respiratory (inhalation)
Prices
Unit description Cost Unit
Relenza Diskhaler 20 5 mg/blister Aerosol Inhaler 75.73 USD inhaler
Relenza 5 mg diskhaler 3.54 USD each
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents
Country Patent Number Approved Expires (estimated)
United States 6294572 1994-12-15 2014-12-15
United States 5360817 1993-07-26 2013-07-26
Canada 2291994 2003-10-14 2011-04-24
Canada 2081356 2000-02-22 2011-04-24
Properties
State solid
Experimental Properties
Property Value Source
logP -3 Not Available
Predicted Properties
Property Value Source
water solubility 7.31e+00 g/l ALOGPS
logP -2.3 ALOGPS
logP -5.8 ChemAxon
logS -1.7 ALOGPS
pKa (strongest acidic) 3.25 ChemAxon
pKa (strongest basic) 11.93 ChemAxon
physiological charge 0 ChemAxon
hydrogen acceptor count 10 ChemAxon
hydrogen donor count 7 ChemAxon
polar surface area 200.72 ChemAxon
rotatable bond count 6 ChemAxon
refractivity 76.19 ChemAxon
polarizability 31.24 ChemAxon
References
Synthesis Reference Not Available
General Reference
  1. 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
  2. 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
  3. 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
  4. 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
External Links
Resource Link
KEGG Drug D00902 Link_out
KEGG Compound C08095 Link_out
PubChem Compound 60855 Link_out
PubChem Substance 46508581 Link_out
ChemSpider 54842 Link_out
BindingDB 4934 Link_out
ChEBI 50663 Link_out
ChEMBL 50663 Link_out
Therapeutic Targets Database DAP000715 Link_out
PharmGKB PA164740891 Link_out
HET ZMR Link_out
Drug Product Database 2240863 Link_out
RxList http://www.rxlist.com/cgi/generic2/zanam.htm Link_out
Drugs.com http://www.drugs.com/cdi/zanamivir.html Link_out
Wikipedia http://en.wikipedia.org/wiki/Zanamivir Link_out
ATC Codes
  • J05AH01
AHFS Codes
  • 08:18.28
PDB Entries
FDA label show (36.7 KB)
MSDS show (53.6 KB)
Interactions
Drug Interactions Not Available
Food Interactions Not Available
Targets

1. Neuraminidase

Pharmacological action: yes
Actions: inhibitor

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

Organism class: viral
UniProt ID: P06818 Link_out
Gene: NA
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. 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
  2. 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
  3. 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
  4. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. Pubmed

2. Neuraminidase

Pharmacological action: yes
Actions: inhibitor

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)

Organism class: viral
UniProt ID: P27907 Link_out
Gene: NA
Protein Sequence: FASTA
SNPs: SNPJam Report Link_out

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
  2. Oakley AJ, Barrett S, Peat TS, Newman J, Streltsov VA, Waddington L, Saito T, Tashiro M, McKimm-Breschkin JL: Structural and Functional Basis of Resistance to Neuraminidase Inhibitors of Influenza B Viruses. J Med Chem. 2010 Aug 9. Pubmed

3. Sialidase-2

Pharmacological action: unknown
Actions: inhibitor

Hydrolyzes sialylated compounds

Organism class: human
UniProt ID: Q9Y3R4 Link_out
Gene: NEU2
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Chavas LM, Kato R, Suzuki N, von Itzstein M, Mann MC, Thomson RJ, Dyason JC, McKimm-Breschkin J, Fusi P, Tringali C, Venerando B, Tettamanti G, Monti E, Wakatsuki S: Complexity in influenza virus targeted drug design: interaction with human sialidases. J Med Chem. 2010 Apr 8;53(7):2998-3002. Pubmed
Comments
Drug created on June 13, 2005 07:24 / Updated on February 08, 2013 16:19