Inhibition of Viral Adhesion and Infection by Sialic-Acid-Conjugated Dendritic Polymers
Identifieur interne : 001994 ( Main/Exploration ); précédent : 001993; suivant : 001995Inhibition of Viral Adhesion and Infection by Sialic-Acid-Conjugated Dendritic Polymers
Auteurs : Jon D. Reuter [États-Unis] ; Andrzej Myc [États-Unis] ; Michael M. Hayes [États-Unis] ; Zhonghong Gan [États-Unis] ; Rene Roy [États-Unis] ; Dujie Qin [États-Unis] ; Rui Yin [États-Unis] ; Lars T. Piehler [États-Unis] ; Roseita Esfand [États-Unis] ; Donald A. Tomalia [États-Unis] ; James R. Baker [États-Unis]Source :
- Bioconjugate Chemistry [ 1043-1802 ] ; 1999.
Descripteurs français
- KwdFr :
- Acides sialiques (pharmacologie), Acides sialiques (synthèse chimique), Adhérence cellulaire (), Animaux, Anticorps antiviraux, Embryon de poulet, Furets, Glycoconjugués (pharmacologie), Glycoconjugués (synthèse chimique), Poulets, Résines acryliques (), Résines acryliques (pharmacologie), Résines acryliques (synthèse chimique), Souris, Tests d'inhibition de l'hémagglutination, Virus de la grippe A (), Virus de la grippe A (immunologie), Virus de la grippe A (physiologie), Érythrocytes (virologie).
- MESH :
- immunologie : Virus de la grippe A.
- pharmacologie : Acides sialiques, Glycoconjugués, Résines acryliques.
- physiologie : Virus de la grippe A.
- synthèse chimique : Acides sialiques, Glycoconjugués, Résines acryliques.
- virologie : Érythrocytes.
- Adhérence cellulaire, Animaux, Anticorps antiviraux, Embryon de poulet, Furets, Poulets, Résines acryliques, Souris, Tests d'inhibition de l'hémagglutination, Virus de la grippe A.
English descriptors
- KwdEn :
- Acrylic Resins (chemical synthesis), Acrylic Resins (chemistry), Acrylic Resins (pharmacology), Animals, Antibodies, Viral, Cell Adhesion (drug effects), Chick Embryo, Chickens, Erythrocytes (virology), Ferrets, Glycoconjugates (chemical synthesis), Glycoconjugates (pharmacology), Hemagglutination Inhibition Tests, Influenza A virus (drug effects), Influenza A virus (immunology), Influenza A virus (physiology), Mice, Sialic Acids (chemical synthesis), Sialic Acids (pharmacology).
- MESH :
- chemical , chemical synthesis : Acrylic Resins, Glycoconjugates, Sialic Acids.
- chemical , chemistry : Acrylic Resins.
- chemical , pharmacology : Acrylic Resins, Glycoconjugates, Sialic Acids.
- drug effects : Cell Adhesion, Influenza A virus.
- immunology : Influenza A virus.
- physiology : Influenza A virus.
- virology : Erythrocytes.
- Animals, Antibodies, Viral, Chick Embryo, Chickens, Ferrets, Hemagglutination Inhibition Tests, Mice.
Abstract
Multiple sialic acid (SA) residues conjugated to a linear polyacrylamide backbone are more effective than monomeric SA at inhibiting influenza-induced agglutination of red blood cells. However, “polymeric inhibitors” based on polyacrylamide backbones are cytotoxic. Dendritic polymers offer a nontoxic alternative to polyacrylamide and may provide a variety of potential synthetic inhibitors of influenza virus adhesion due to the wide range of available polymer structures. We evaluated several dendritic polymeric inhibitors, including spheroidal, linear, linear-dendron copolymers, comb-branched, and dendrigraft polymers, for the ability to inhibit virus hemagglutination (HA) and to block infection of mammalian cells in vitro. Four viruses were tested: influenza A H2N2 (selectively propagated two ways), X-31 influenza A H3N2, and sendai. The most potent of the linear and spheroidal inhibitors were 32−256-fold more effective than monomeric SA at inhibiting HA by the H2N2 influenza virus. Linear-dendron copolymers were 1025−8200-fold more effective against H2N2 influenza, X-31 influenza, and sendai viruses. The most effective were the comb-branched and dendrigraft inhibitors, which showed up to 50000-fold increased activity against these viruses. We were able to demonstrate significant (p < 0.001) dose-dependent reduction of influenza infection in mammalian cells by polymeric inhibitors, the first such demonstration for multivalent SA inhibitors. Effective dendrimer polymers were not cytotoxic to mammalian cells at therapeutic levels. Of additional interest, variation in the inhibitory effect was observed with different viruses, suggesting possible differences due to specific growth conditions of virus. SA-conjugated dendritic polymers may provide a new therapeutic modality for viruses that employ SA as their target receptor.
Url:
DOI: 10.1021/bc980099n
Affiliations:
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Le document en format XML
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<term>Acrylic Resins (pharmacology)</term>
<term>Animals</term>
<term>Antibodies, Viral</term>
<term>Cell Adhesion (drug effects)</term>
<term>Chick Embryo</term>
<term>Chickens</term>
<term>Erythrocytes (virology)</term>
<term>Ferrets</term>
<term>Glycoconjugates (chemical synthesis)</term>
<term>Glycoconjugates (pharmacology)</term>
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<term>Influenza A virus (immunology)</term>
<term>Influenza A virus (physiology)</term>
<term>Mice</term>
<term>Sialic Acids (chemical synthesis)</term>
<term>Sialic Acids (pharmacology)</term>
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<term>Acides sialiques (synthèse chimique)</term>
<term>Adhérence cellulaire ()</term>
<term>Animaux</term>
<term>Anticorps antiviraux</term>
<term>Embryon de poulet</term>
<term>Furets</term>
<term>Glycoconjugués (pharmacologie)</term>
<term>Glycoconjugués (synthèse chimique)</term>
<term>Poulets</term>
<term>Résines acryliques ()</term>
<term>Résines acryliques (pharmacologie)</term>
<term>Résines acryliques (synthèse chimique)</term>
<term>Souris</term>
<term>Tests d'inhibition de l'hémagglutination</term>
<term>Virus de la grippe A ()</term>
<term>Virus de la grippe A (immunologie)</term>
<term>Virus de la grippe A (physiologie)</term>
<term>Érythrocytes (virologie)</term>
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<term>Glycoconjugates</term>
<term>Sialic Acids</term>
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<term>Sialic Acids</term>
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<term>Glycoconjugués</term>
<term>Résines acryliques</term>
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<term>Furets</term>
<term>Poulets</term>
<term>Résines acryliques</term>
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<front><div type="abstract">Multiple sialic acid (SA) residues conjugated to a linear polyacrylamide backbone are more effective than monomeric SA at inhibiting influenza-induced agglutination of red blood cells. However, “polymeric inhibitors” based on polyacrylamide backbones are cytotoxic. Dendritic polymers offer a nontoxic alternative to polyacrylamide and may provide a variety of potential synthetic inhibitors of influenza virus adhesion due to the wide range of available polymer structures. We evaluated several dendritic polymeric inhibitors, including spheroidal, linear, linear-dendron copolymers, comb-branched, and dendrigraft polymers, for the ability to inhibit virus hemagglutination (HA) and to block infection of mammalian cells in vitro. Four viruses were tested: influenza A H2N2 (selectively propagated two ways), X-31 influenza A H3N2, and sendai. The most potent of the linear and spheroidal inhibitors were 32−256-fold more effective than monomeric SA at inhibiting HA by the H2N2 influenza virus. Linear-dendron copolymers were 1025−8200-fold more effective against H2N2 influenza, X-31 influenza, and sendai viruses. The most effective were the comb-branched and dendrigraft inhibitors, which showed up to 50000-fold increased activity against these viruses. We were able to demonstrate significant (p < 0.001) dose-dependent reduction of influenza infection in mammalian cells by polymeric inhibitors, the first such demonstration for multivalent SA inhibitors. Effective dendrimer polymers were not cytotoxic to mammalian cells at therapeutic levels. Of additional interest, variation in the inhibitory effect was observed with different viruses, suggesting possible differences due to specific growth conditions of virus. SA-conjugated dendritic polymers may provide a new therapeutic modality for viruses that employ SA as their target receptor.</div>
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