A hexapeptide of the receptor-binding domain of SARS corona virus spike protein blocks viral entry into host cells via the human receptor ACE2
Identifieur interne : 001F95 ( Main/Exploration ); précédent : 001F94; suivant : 001F96A hexapeptide of the receptor-binding domain of SARS corona virus spike protein blocks viral entry into host cells via the human receptor ACE2
Auteurs : Anna-Winona Struck [Allemagne] ; Marco Axmann [Allemagne] ; Susanne Pfefferle [Allemagne] ; Christian Drosten [Allemagne] ; Bernd Meyer [Allemagne]Source :
- Antiviral research [ 0166-3542 ] ; 2012.
Descripteurs français
- KwdFr :
- Antiviraux (pharmacologie), Glycoprotéine de spicule des coronavirus, Glycoprotéines membranaires (génétique), Glycoprotéines membranaires (pharmacologie), Humains, Liaison aux protéines, Peptides (génétique), Peptides (pharmacologie), Peptidyl-Dipeptidase A (métabolisme), Protéines de l'enveloppe virale (génétique), Protéines de l'enveloppe virale (pharmacologie), Pénétration virale (), Récepteurs viraux (métabolisme), Résonance plasmonique de surface, Virus du SRAS (), Virus du SRAS (croissance et développement), Virus du SRAS (physiologie).
- MESH :
- croissance et développement : Virus du SRAS.
- génétique : Glycoprotéines membranaires, Peptides, Protéines de l'enveloppe virale.
- métabolisme : Peptidyl-Dipeptidase A, Récepteurs viraux.
- pharmacologie : Antiviraux, Glycoprotéines membranaires, Peptides, Protéines de l'enveloppe virale.
- physiologie : Virus du SRAS.
- Pascal (Inist)
- Glycoprotéine de spicule des coronavirus, Humains, Liaison aux protéines, Pénétration virale, Récepteur biologique, Résonance plasmonique de surface, Virus du SRAS, Virus syndrome respiratoire aigu sévère, Protéine, In vitro, Cellule, Homme, Multiplication cellulaire, Criblage, Dépistage, Angiotensin converting enzyme 2, Inhibiteur d'entrée.
- Wicri :
- topic : Homme.
English descriptors
- KwdEn :
- Antiviral Agents (pharmacology), Biological receptor, Cell, Cell proliferation, Entry inhibitor, Human, Humans, In vitro, Medical screening, Membrane Glycoproteins (genetics), Membrane Glycoproteins (pharmacology), Peptides (genetics), Peptides (pharmacology), Peptidyl-Dipeptidase A (metabolism), Protein, Protein Binding, Receptors, Virus (metabolism), SARS Virus (drug effects), SARS Virus (growth & development), SARS Virus (physiology), Screening, Severe acute respiratory syndrome virus, Spike Glycoprotein, Coronavirus, Surface Plasmon Resonance, Viral Envelope Proteins (genetics), Viral Envelope Proteins (pharmacology), Virus Internalization (drug effects).
- MESH :
- chemical , genetics : Membrane Glycoproteins, Peptides, Viral Envelope Proteins.
- chemical , metabolism : Peptidyl-Dipeptidase A, Receptors, Virus.
- chemical , pharmacology : Antiviral Agents, Membrane Glycoproteins, Peptides, Viral Envelope Proteins.
- drug effects : SARS Virus, Virus Internalization.
- growth & development : SARS Virus.
- physiology : SARS Virus.
- Humans, Protein Binding, Spike Glycoprotein, Coronavirus, Surface Plasmon Resonance.
Abstract
In vitro infection of Vero E6 cells by SARS coronavirus (SARS-CoV) is blocked by hexapeptide Tyr-Lys-Tyr-Arg-Tyr-Leu. The peptide also inhibits proliferation of coronavirus NL63. On human cells both viruses utilize angiotensin-converting enzyme 2 (ACE2) as entry receptor. Blocking the viral entry is specific as alpha virus Sindbis shows no reduction in infectivity. Peptide 438YKYRYL443 is part of the receptor-binding domain (RBD) of the spike protein of SARS-CoV. Peptide libraries were screened by surface plasmon resonance (SPR) to identify RBD binding epitopes. 438YKYRYL443 carries the dominant binding epitope and binds to ACE2 with KD = 46 μM. The binding mode was further characterized by saturation transfer difference (STD) NMR spectroscopy and molecular dynamic simulations. Based on this information the peptide can be used as lead structure to design potential entry inhibitors against SARS-CoV and related viruses.
Url:
Affiliations:
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Le document en format XML
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<series><title level="j" type="main">Antiviral research</title>
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<profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Antiviral Agents (pharmacology)</term>
<term>Biological receptor</term>
<term>Cell</term>
<term>Cell proliferation</term>
<term>Entry inhibitor</term>
<term>Human</term>
<term>Humans</term>
<term>In vitro</term>
<term>Medical screening</term>
<term>Membrane Glycoproteins (genetics)</term>
<term>Membrane Glycoproteins (pharmacology)</term>
<term>Peptides (genetics)</term>
<term>Peptides (pharmacology)</term>
<term>Peptidyl-Dipeptidase A (metabolism)</term>
<term>Protein</term>
<term>Protein Binding</term>
<term>Receptors, Virus (metabolism)</term>
<term>SARS Virus (drug effects)</term>
<term>SARS Virus (growth & development)</term>
<term>SARS Virus (physiology)</term>
<term>Screening</term>
<term>Severe acute respiratory syndrome virus</term>
<term>Spike Glycoprotein, Coronavirus</term>
<term>Surface Plasmon Resonance</term>
<term>Viral Envelope Proteins (genetics)</term>
<term>Viral Envelope Proteins (pharmacology)</term>
<term>Virus Internalization (drug effects)</term>
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<keywords scheme="KwdFr" xml:lang="fr"><term>Antiviraux (pharmacologie)</term>
<term>Glycoprotéine de spicule des coronavirus</term>
<term>Glycoprotéines membranaires (génétique)</term>
<term>Glycoprotéines membranaires (pharmacologie)</term>
<term>Humains</term>
<term>Liaison aux protéines</term>
<term>Peptides (génétique)</term>
<term>Peptides (pharmacologie)</term>
<term>Peptidyl-Dipeptidase A (métabolisme)</term>
<term>Protéines de l'enveloppe virale (génétique)</term>
<term>Protéines de l'enveloppe virale (pharmacologie)</term>
<term>Pénétration virale ()</term>
<term>Récepteurs viraux (métabolisme)</term>
<term>Résonance plasmonique de surface</term>
<term>Virus du SRAS ()</term>
<term>Virus du SRAS (croissance et développement)</term>
<term>Virus du SRAS (physiologie)</term>
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<keywords scheme="MESH" type="chemical" qualifier="genetics" xml:lang="en"><term>Membrane Glycoproteins</term>
<term>Peptides</term>
<term>Viral Envelope Proteins</term>
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<keywords scheme="MESH" type="chemical" qualifier="metabolism" xml:lang="en"><term>Peptidyl-Dipeptidase A</term>
<term>Receptors, Virus</term>
</keywords>
<keywords scheme="MESH" type="chemical" qualifier="pharmacology" xml:lang="en"><term>Antiviral Agents</term>
<term>Membrane Glycoproteins</term>
<term>Peptides</term>
<term>Viral Envelope Proteins</term>
</keywords>
<keywords scheme="MESH" qualifier="croissance et développement" xml:lang="fr"><term>Virus du SRAS</term>
</keywords>
<keywords scheme="MESH" qualifier="drug effects" xml:lang="en"><term>SARS Virus</term>
<term>Virus Internalization</term>
</keywords>
<keywords scheme="MESH" qualifier="growth & development" xml:lang="en"><term>SARS Virus</term>
</keywords>
<keywords scheme="MESH" qualifier="génétique" xml:lang="fr"><term>Glycoprotéines membranaires</term>
<term>Peptides</term>
<term>Protéines de l'enveloppe virale</term>
</keywords>
<keywords scheme="MESH" qualifier="métabolisme" xml:lang="fr"><term>Peptidyl-Dipeptidase A</term>
<term>Récepteurs viraux</term>
</keywords>
<keywords scheme="MESH" qualifier="pharmacologie" xml:lang="fr"><term>Antiviraux</term>
<term>Glycoprotéines membranaires</term>
<term>Peptides</term>
<term>Protéines de l'enveloppe virale</term>
</keywords>
<keywords scheme="MESH" qualifier="physiologie" xml:lang="fr"><term>Virus du SRAS</term>
</keywords>
<keywords scheme="MESH" qualifier="physiology" xml:lang="en"><term>SARS Virus</term>
</keywords>
<keywords scheme="MESH" xml:lang="en"><term>Humans</term>
<term>Protein Binding</term>
<term>Spike Glycoprotein, Coronavirus</term>
<term>Surface Plasmon Resonance</term>
</keywords>
<keywords scheme="Pascal" xml:lang="fr"><term>Glycoprotéine de spicule des coronavirus</term>
<term>Humains</term>
<term>Liaison aux protéines</term>
<term>Pénétration virale</term>
<term>Récepteur biologique</term>
<term>Résonance plasmonique de surface</term>
<term>Virus du SRAS</term>
<term>Virus syndrome respiratoire aigu sévère</term>
<term>Protéine</term>
<term>In vitro</term>
<term>Cellule</term>
<term>Homme</term>
<term>Multiplication cellulaire</term>
<term>Criblage</term>
<term>Dépistage</term>
<term>Angiotensin converting enzyme 2</term>
<term>Inhibiteur d'entrée</term>
</keywords>
<keywords scheme="Wicri" type="topic" xml:lang="fr"><term>Homme</term>
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<front><div type="abstract" xml:lang="en">In vitro infection of Vero E6 cells by SARS coronavirus (SARS-CoV) is blocked by hexapeptide Tyr-Lys-Tyr-Arg-Tyr-Leu. The peptide also inhibits proliferation of coronavirus NL63. On human cells both viruses utilize angiotensin-converting enzyme 2 (ACE2) as entry receptor. Blocking the viral entry is specific as alpha virus Sindbis shows no reduction in infectivity. Peptide <sup>438</sup>
YKYRYL<sup>443</sup>
is part of the receptor-binding domain (RBD) of the spike protein of SARS-CoV. Peptide libraries were screened by surface plasmon resonance (SPR) to identify RBD binding epitopes. <sup>438</sup>
YKYRYL<sup>443</sup>
carries the dominant binding epitope and binds to ACE2 with K<sub>D</sub>
= 46 μM. The binding mode was further characterized by saturation transfer difference (STD) NMR spectroscopy and molecular dynamic simulations. Based on this information the peptide can be used as lead structure to design potential entry inhibitors against SARS-CoV and related viruses.</div>
</front>
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<affiliations><list><country><li>Allemagne</li>
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<name sortKey="Drosten, Christian" sort="Drosten, Christian" uniqKey="Drosten C" first="Christian" last="Drosten">Christian Drosten</name>
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