Synthetic peptides outside the spike protein heptad repeat regions as potent inhibitors of SARS-associated coronavirus.
Identifieur interne : 000F76 ( Ncbi/Curation ); précédent : 000F75; suivant : 000F77Synthetic peptides outside the spike protein heptad repeat regions as potent inhibitors of SARS-associated coronavirus.
Auteurs : Bo-Jion Zheng [République populaire de Chine] ; Yi Guan ; Ming-Liang Hez ; Hongzhe Sun ; Lanying Du ; Ying Zheng ; Kin-Ling Wong ; Honglin Chen ; Ying Chen ; Linyu Lu ; Julian A. Tanner ; Rory M. Watt ; Neri Niccolai ; Andrea Bernini ; Ottavia Spiga ; Patrick C Y. Woo ; Hsiang-Fu Kung ; Kwok-Yung Yuen ; Jian-Dong HuangSource :
- Antiviral therapy [ 1359-6535 ] ; 2005.
Descripteurs français
- KwdFr :
- Animaux, Antiviraux (), Antiviraux (pharmacologie), Conformation des protéines, Données de séquences moléculaires, Glycoprotéine de spicule des coronavirus, Glycoprotéines membranaires (), Humains, Lignée cellulaire, Peptides (), Peptides (pharmacologie), Protéines de l'enveloppe virale (), Relation dose-effet des médicaments, Séquence d'acides aminés, Virus du SRAS ().
- MESH :
- pharmacologie : Antiviraux, Peptides.
- Animaux, Antiviraux, Conformation des protéines, Données de séquences moléculaires, Glycoprotéine de spicule des coronavirus, Glycoprotéines membranaires, Humains, Lignée cellulaire, Peptides, Protéines de l'enveloppe virale, Relation dose-effet des médicaments, Séquence d'acides aminés, Virus du SRAS.
English descriptors
- KwdEn :
- Amino Acid Sequence, Animals, Antiviral Agents (chemistry), Antiviral Agents (pharmacology), Cell Line, Dose-Response Relationship, Drug, Humans, Membrane Glycoproteins (chemistry), Molecular Sequence Data, Peptides (chemistry), Peptides (pharmacology), Protein Conformation, SARS Virus (drug effects), Spike Glycoprotein, Coronavirus, Viral Envelope Proteins (chemistry).
- MESH :
- chemical , chemistry : Antiviral Agents, Membrane Glycoproteins, Peptides, Viral Envelope Proteins.
- chemical , pharmacology : Antiviral Agents, Peptides.
- drug effects : SARS Virus.
- Amino Acid Sequence, Animals, Cell Line, Dose-Response Relationship, Drug, Humans, Molecular Sequence Data, Protein Conformation, Spike Glycoprotein, Coronavirus.
Abstract
A novel severe acute respiratory syndrome (SARS)-associated coronavirus (SARS-CoV) has been identified as the aetiological agent of SARS. We previously isolated and characterized SARS-CoV and SARS-CoV-like viruses from human and animals, respectively, suggesting that SARS could be transmitted from wild/farmed animals to humans. Comparison of the viral genomes indicated that sequence variation between animal and human isolates existed mainly in the spike (S) gene. We hypothesized that these variations may underlie a change of binding specificity of the S protein to the host cells, permitting viral transmission from animals to humans. Here we report that four 20-mer synthetic peptides (S protein fragments), designed to span these sequence variation hotspots, exhibited significant antiviral activities in a cell line. SARS-CoV infectivity was reduced over 10 000-fold through pre-incubation with two of these peptides, while it was completely inhibited in the presence of three peptides. Molecular modelling of the SARS-CoV peplomer suggests that three of these antiviral peptides map to the interfaces between the three monomers of the trimeric peplomer rather than the heptad repeat region from which short peptides are known to inhibit viral entry. Our results revealed novel regions in the spike protein that can be targeted to inhibit viral infection. The peptides identified in this study could be further developed into antiviral drugs.
PubMed: 15918330
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<affiliation wicri:level="1"><nlm:affiliation>Department of Microbiology, University of Hong Kong, Pokfulam, Hong Kong SAR, China. bzheng@hkucc.hku.hk</nlm:affiliation>
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<term>Antiviraux (pharmacologie)</term>
<term>Conformation des protéines</term>
<term>Données de séquences moléculaires</term>
<term>Glycoprotéine de spicule des coronavirus</term>
<term>Glycoprotéines membranaires ()</term>
<term>Humains</term>
<term>Lignée cellulaire</term>
<term>Peptides ()</term>
<term>Peptides (pharmacologie)</term>
<term>Protéines de l'enveloppe virale ()</term>
<term>Relation dose-effet des médicaments</term>
<term>Séquence d'acides aminés</term>
<term>Virus du SRAS ()</term>
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<term>Cell Line</term>
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<term>Molecular Sequence Data</term>
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<term>Glycoprotéine de spicule des coronavirus</term>
<term>Glycoprotéines membranaires</term>
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<term>Lignée cellulaire</term>
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<front><div type="abstract" xml:lang="en">A novel severe acute respiratory syndrome (SARS)-associated coronavirus (SARS-CoV) has been identified as the aetiological agent of SARS. We previously isolated and characterized SARS-CoV and SARS-CoV-like viruses from human and animals, respectively, suggesting that SARS could be transmitted from wild/farmed animals to humans. Comparison of the viral genomes indicated that sequence variation between animal and human isolates existed mainly in the spike (S) gene. We hypothesized that these variations may underlie a change of binding specificity of the S protein to the host cells, permitting viral transmission from animals to humans. Here we report that four 20-mer synthetic peptides (S protein fragments), designed to span these sequence variation hotspots, exhibited significant antiviral activities in a cell line. SARS-CoV infectivity was reduced over 10 000-fold through pre-incubation with two of these peptides, while it was completely inhibited in the presence of three peptides. Molecular modelling of the SARS-CoV peplomer suggests that three of these antiviral peptides map to the interfaces between the three monomers of the trimeric peplomer rather than the heptad repeat region from which short peptides are known to inhibit viral entry. Our results revealed novel regions in the spike protein that can be targeted to inhibit viral infection. The peptides identified in this study could be further developed into antiviral drugs.</div>
</front>
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