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 : 001366 ( Main/Exploration ); précédent : 001365; suivant : 001367A 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
- Pascal (Inist)
- Wicri :
- topic : Homme.
English descriptors
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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.
Affiliations:
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last="Axmann">Marco Axmann</name><affiliation wicri:level="1"><inist:fA14 i1="01"><s1>Organic Chemistry, Department of Chemistry, Faculty of Sciences, University of Hamburg, Martin Luther King Place 6</s1><s2>20146 Hamburg</s2><s3>DEU</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>5 aut.</sZ></inist:fA14><country>Allemagne</country><wicri:noRegion>20146 Hamburg</wicri:noRegion><placeName><settlement type="city">Hambourg</settlement><region type="land" nuts="2">Hambourg</region></placeName></affiliation></author><author><name sortKey="Pfefferle, Susanne" sort="Pfefferle, Susanne" uniqKey="Pfefferle S" first="Susanne" last="Pfefferle">Susanne Pfefferle</name><affiliation wicri:level="1"><inist:fA14 i1="02"><s1>Department of Virology, Bernhard Nocht Institute for Tropical Medicine, Bernhard-Nocht-Str. 74</s1><s2>20359 Hamburg</s2><s3>DEU</s3><sZ>3 aut.</sZ><sZ>4 aut.</sZ></inist:fA14><country>Allemagne</country><wicri:noRegion>20359 Hamburg</wicri:noRegion><placeName><settlement type="city">Hambourg</settlement><region type="land" nuts="2">Hambourg</region></placeName></affiliation></author><author><name sortKey="Drosten, Christian" sort="Drosten, Christian" uniqKey="Drosten C" first="Christian" last="Drosten">Christian Drosten</name><affiliation wicri:level="1"><inist:fA14 i1="02"><s1>Department of Virology, Bernhard Nocht Institute for Tropical Medicine, Bernhard-Nocht-Str. 74</s1><s2>20359 Hamburg</s2><s3>DEU</s3><sZ>3 aut.</sZ><sZ>4 aut.</sZ></inist:fA14><country>Allemagne</country><wicri:noRegion>20359 Hamburg</wicri:noRegion><placeName><settlement type="city">Hambourg</settlement><region type="land" nuts="2">Hambourg</region></placeName></affiliation></author><author><name sortKey="Meyer, Bernd" sort="Meyer, Bernd" uniqKey="Meyer B" first="Bernd" last="Meyer">Bernd Meyer</name><affiliation wicri:level="1"><inist:fA14 i1="01"><s1>Organic Chemistry, Department of Chemistry, Faculty of Sciences, University of Hamburg, Martin Luther King Place 6</s1><s2>20146 Hamburg</s2><s3>DEU</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>5 aut.</sZ></inist:fA14><country>Allemagne</country><wicri:noRegion>20146 Hamburg</wicri:noRegion><placeName><settlement type="city">Hambourg</settlement><region type="land" nuts="2">Hambourg</region></placeName></affiliation></author></analytic><series><title level="j" type="main">Antiviral research</title><title level="j" type="abbreviated">Antivir. res.</title><idno type="ISSN">0166-3542</idno><imprint><date when="2012">2012</date></imprint></series></biblStruct></sourceDesc><seriesStmt><title level="j" type="main">Antiviral research</title><title level="j" type="abbreviated">Antivir. res.</title><idno type="ISSN">0166-3542</idno></seriesStmt></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Biological receptor</term><term>Cell</term><term>Cell proliferation</term><term>Entry inhibitor</term><term>Human</term><term>In vitro</term><term>Medical screening</term><term>Protein</term><term>Screening</term><term>Severe acute respiratory syndrome virus</term></keywords><keywords scheme="Pascal" xml:lang="fr"><term>Récepteur biologique</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></keywords></textClass></profileDesc></teiHeader><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></TEI><affiliations><list><country><li>Allemagne</li></country><region><li>Hambourg</li></region><settlement><li>Hambourg</li></settlement></list><tree><country name="Allemagne"><region name="Hambourg"><name sortKey="Struck, Anna Winona" sort="Struck, Anna Winona" uniqKey="Struck A" first="Anna-Winona" last="Struck">Anna-Winona Struck</name></region><name sortKey="Axmann, Marco" sort="Axmann, Marco" uniqKey="Axmann M" first="Marco" last="Axmann">Marco Axmann</name><name sortKey="Drosten, Christian" sort="Drosten, Christian" uniqKey="Drosten C" first="Christian" last="Drosten">Christian Drosten</name><name sortKey="Meyer, Bernd" sort="Meyer, Bernd" uniqKey="Meyer B" first="Bernd" last="Meyer">Bernd Meyer</name><name sortKey="Pfefferle, Susanne" sort="Pfefferle, Susanne" uniqKey="Pfefferle S" first="Susanne" last="Pfefferle">Susanne Pfefferle</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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