Development of neuraminidase inhibitors as anti‐influenza virus drugs
Identifieur interne : 001674 ( Istex/Curation ); précédent : 001673; suivant : 001675Development of neuraminidase inhibitors as anti‐influenza virus drugs
Auteurs : Joseph N. Varghese [Australie]Source :
- Drug Development Research [ 0272-4391 ] ; 1999-03.
Abstract
Structure‐based design and synthesis of potent influenza virus neuraminidase inhibitors are now being evaluated in human trials as anti‐influenza virus drugs. The first drug of this class, Relenza™ (Zanamivir/GG167), is now awaiting pharmaceutical evaluation and registration in Australia, Europe, and North America for both treatment and prophylaxis of influenza. The target for the drug is the active site of neuraminidase, which is a pocket that has been totally conserved in both Type A and B influenza in all known subtypes of influenza (animal and human). Mutations in residues that surround this conserved pocket allow the virus to escape binding to circulating antibodies that recognise the molecular surface around the active site of the wild‐type virus. High‐affinity neuraminidase inhibitors have been designed that interact only with the conserved active site residues. The design of these sialic acid analogues was based on the crystal structure of influenza virus neuraminidase and its complex with N‐acetyl neuraminic acid (sialic acid) and 2‐deoxy‐2,3‐dehydro‐N‐acetyl neuraminic acid. These novel inhibitors are highly specific for influenza neuraminidase, and have been shown to inhibit influenza virus replication in both cell culture and animal models. The development of drugs against a rapidly mutating organism like influenza has to address to the possibility of emerging drug resistance. This is examined in the light of drug resistant mutants selected after in vitro passaging of virus in the presence of neuraminidase inhibitors. Drug Dev. Res. 46:176–196, 1999. © 1999 Wiley‐Liss, Inc.
Url:
DOI: 10.1002/(SICI)1098-2299(199903/04)46:3/4<176::AID-DDR4>3.0.CO;2-6
Links toward previous steps (curation, corpus...)
- to stream Istex, to step Corpus: Pour aller vers cette notice dans l'étape Curation :001674
Links to Exploration step
ISTEX:D278CB41B6488D1E899E112332E3EB59889CA5FFLe document en format XML
<record><TEI wicri:istexFullTextTei="biblStruct"><teiHeader><fileDesc><titleStmt><title xml:lang="en">Development of neuraminidase inhibitors as anti‐influenza virus drugs</title><author><name sortKey="Varghese, Joseph N" sort="Varghese, Joseph N" uniqKey="Varghese J" first="Joseph N." last="Varghese">Joseph N. Varghese</name><affiliation wicri:level="1"><mods:affiliation>Biomolecular Research Institute, Parkville, Victoria, Australia</mods:affiliation><country xml:lang="fr">Australie</country><wicri:regionArea>Biomolecular Research Institute, Parkville, Victoria</wicri:regionArea></affiliation><affiliation wicri:level="1"><mods:affiliation>E-mail: jose@bioresi.com.au</mods:affiliation><country wicri:rule="url">Australie</country></affiliation><affiliation wicri:level="1"><mods:affiliation>Correspondence address: Biomolecular Research Institute, 343 Royal Parade, Parkville, Victoria 3052, Australia</mods:affiliation><country xml:lang="fr">Australie</country><wicri:regionArea>Correspondence address: Biomolecular Research Institute, 343 Royal Parade, Parkville, Victoria 3052</wicri:regionArea></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">ISTEX</idno><idno type="RBID">ISTEX:D278CB41B6488D1E899E112332E3EB59889CA5FF</idno><date when="1999" year="1999">1999</date><idno type="doi">10.1002/(SICI)1098-2299(199903/04)46:3/4<176::AID-DDR4>3.0.CO;2-6</idno><idno type="url">https://api.istex.fr/ark:/67375/WNG-VV4CKQ2F-F/fulltext.pdf</idno><idno type="wicri:Area/Istex/Corpus">001674</idno><idno type="wicri:explorRef" wicri:stream="Istex" wicri:step="Corpus" wicri:corpus="ISTEX">001674</idno><idno type="wicri:Area/Istex/Curation">001674</idno></publicationStmt><sourceDesc><biblStruct><analytic><title level="a" type="main">Development of neuraminidase inhibitors as anti‐influenza virus drugs</title><author><name sortKey="Varghese, Joseph N" sort="Varghese, Joseph N" uniqKey="Varghese J" first="Joseph N." last="Varghese">Joseph N. Varghese</name><affiliation wicri:level="1"><mods:affiliation>Biomolecular Research Institute, Parkville, Victoria, Australia</mods:affiliation><country xml:lang="fr">Australie</country><wicri:regionArea>Biomolecular Research Institute, Parkville, Victoria</wicri:regionArea></affiliation><affiliation wicri:level="1"><mods:affiliation>E-mail: jose@bioresi.com.au</mods:affiliation><country wicri:rule="url">Australie</country></affiliation><affiliation wicri:level="1"><mods:affiliation>Correspondence address: Biomolecular Research Institute, 343 Royal Parade, Parkville, Victoria 3052, Australia</mods:affiliation><country xml:lang="fr">Australie</country><wicri:regionArea>Correspondence address: Biomolecular Research Institute, 343 Royal Parade, Parkville, Victoria 3052</wicri:regionArea></affiliation></author></analytic><monogr></monogr><series><title level="j" type="main">Drug Development Research</title><title level="j" type="sub">Biotechnology and Pharmacology in Australia</title><title level="j" type="alt">DRUG DEVELOPMENT RESEARCH</title><idno type="ISSN">0272-4391</idno><idno type="eISSN">1098-2299</idno><imprint><biblScope unit="vol">46</biblScope><biblScope unit="issue">3‐4</biblScope><biblScope unit="page" from="176">176</biblScope><biblScope unit="page" to="196">196</biblScope><biblScope unit="page-count">21</biblScope><publisher>John Wiley & Sons, Inc.</publisher><pubPlace>New York</pubPlace><date type="published" when="1999-03">1999-03</date></imprint><idno type="ISSN">0272-4391</idno></series></biblStruct></sourceDesc><seriesStmt><idno type="ISSN">0272-4391</idno></seriesStmt></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">Structure‐based design and synthesis of potent influenza virus neuraminidase inhibitors are now being evaluated in human trials as anti‐influenza virus drugs. The first drug of this class, Relenza™ (Zanamivir/GG167), is now awaiting pharmaceutical evaluation and registration in Australia, Europe, and North America for both treatment and prophylaxis of influenza. The target for the drug is the active site of neuraminidase, which is a pocket that has been totally conserved in both Type A and B influenza in all known subtypes of influenza (animal and human). Mutations in residues that surround this conserved pocket allow the virus to escape binding to circulating antibodies that recognise the molecular surface around the active site of the wild‐type virus. High‐affinity neuraminidase inhibitors have been designed that interact only with the conserved active site residues. The design of these sialic acid analogues was based on the crystal structure of influenza virus neuraminidase and its complex with N‐acetyl neuraminic acid (sialic acid) and 2‐deoxy‐2,3‐dehydro‐N‐acetyl neuraminic acid. These novel inhibitors are highly specific for influenza neuraminidase, and have been shown to inhibit influenza virus replication in both cell culture and animal models. The development of drugs against a rapidly mutating organism like influenza has to address to the possibility of emerging drug resistance. This is examined in the light of drug resistant mutants selected after in vitro passaging of virus in the presence of neuraminidase inhibitors. Drug Dev. Res. 46:176–196, 1999. © 1999 Wiley‐Liss, Inc.</div></front></TEI></record>Pour manipuler ce document sous Unix (Dilib)
EXPLOR_STEP=$WICRI_ROOT/Sante/explor/H2N2V1/Data/Istex/Curation
HfdSelect -h $EXPLOR_STEP/biblio.hfd -nk 001674 | SxmlIndent | more
Ou
HfdSelect -h $EXPLOR_AREA/Data/Istex/Curation/biblio.hfd -nk 001674 | SxmlIndent | more
Pour mettre un lien sur cette page dans le réseau Wicri
{{Explor lien
|wiki= Sante
|area= H2N2V1
|flux= Istex
|étape= Curation
|type= RBID
|clé= ISTEX:D278CB41B6488D1E899E112332E3EB59889CA5FF
|texte= Development of neuraminidase inhibitors as anti‐influenza virus drugs
}}
| This area was generated with Dilib version V0.6.33. |  |