SrasV1, Main, Exploration, bibRecord, 004D49

Synthetic peptides outside the spike protein heptad repeat regions as potent inhibitors of SARS-associated coronavirus

Identifieur interne : 004D49 ( Main/Exploration ); précédent : 004D48; suivant : 004D50

Synthetic peptides outside the spike protein heptad repeat regions as potent inhibitors of SARS-associated coronavirus

Auteurs : Bo-Jian Zheng [Hong Kong] ; YI GUAN [Hong Kong] ; Ming-Liang He [Hong Kong] ; HONGZHE SUN [Hong Kong] ; LANYING DU [Hong Kong] ; YING ZHENG [Hong Kong] ; Kin-Ling Wong [Hong Kong] ; HONGLIN CHEN [Hong Kong] ; YING CHEN [Hong Kong] ; LINYU LU [Hong Kong] ; Julian A. Tanner [Hong Kong] ; Rory M. Watt [Hong Kong] ; Neri Niccolai [Italie] ; Andrea Bernini [Italie] ; Ottavia Spiga [Italie] ; Patrick C. Y. Woo [Hong Kong] ; Hsiang-Fu Kung [Hong Kong] ; Kwok-Yung Yuen [Hong Kong] ; Jian-Dong Huang [Hong Kong]

Source :

Antiviral therapy : (London) [ 1359-6535 ] ; 2005.

RBID : Pascal:05-0250654

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.
Pascal (Inist)
- Animaux, Antiviraux, Conformation des protéines, Données de séquences moléculaires, Glycoprotéine de spicule des coronavirus, Glycoprotéines membranaires, Humains, Lignée cellulaire, Peptide, Peptides, Protéine, Protéines de l'enveloppe virale, Relation dose-effet des médicaments, Séquence d'acides aminés, Virus du SRAS, Virus syndrome respiratoire aigu sévère.

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, Peptides (chemistry), Peptides (pharmacology), Protein, Protein Conformation, SARS Virus (drug effects), Severe acute respiratory syndrome virus, 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 10000-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.

Affiliations:

Le document en format XML

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<sZ>6 aut.</sZ>
<sZ>7 aut.</sZ>
<sZ>8 aut.</sZ>
<sZ>9 aut.</sZ>
<sZ>16 aut.</sZ>
<sZ>18 aut.</sZ>
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</affiliation>
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<author><name sortKey="Ying Zheng" sort="Ying Zheng" uniqKey="Ying Zheng" last="Ying Zheng">YING ZHENG</name>
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<s3>HKG</s3>
<sZ>1 aut.</sZ>
<sZ>2 aut.</sZ>
<sZ>5 aut.</sZ>
<sZ>6 aut.</sZ>
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<sZ>9 aut.</sZ>
<sZ>16 aut.</sZ>
<sZ>18 aut.</sZ>
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<country>Hong Kong</country>
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</affiliation>
</author>
<author><name sortKey="Wong, Kin Ling" sort="Wong, Kin Ling" uniqKey="Wong K" first="Kin-Ling" last="Wong">Kin-Ling Wong</name>
<affiliation wicri:level="1"><inist:fA14 i1="01"><s1>Department of Microbiology, University of Hong Kong</s1>
<s2>Pokfulam</s2>
<s3>HKG</s3>
<sZ>1 aut.</sZ>
<sZ>2 aut.</sZ>
<sZ>5 aut.</sZ>
<sZ>6 aut.</sZ>
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<sZ>9 aut.</sZ>
<sZ>16 aut.</sZ>
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</affiliation>
</author>
<author><name sortKey="Honglin Chen" sort="Honglin Chen" uniqKey="Honglin Chen" last="Honglin Chen">HONGLIN CHEN</name>
<affiliation wicri:level="1"><inist:fA14 i1="01"><s1>Department of Microbiology, University of Hong Kong</s1>
<s2>Pokfulam</s2>
<s3>HKG</s3>
<sZ>1 aut.</sZ>
<sZ>2 aut.</sZ>
<sZ>5 aut.</sZ>
<sZ>6 aut.</sZ>
<sZ>7 aut.</sZ>
<sZ>8 aut.</sZ>
<sZ>9 aut.</sZ>
<sZ>16 aut.</sZ>
<sZ>18 aut.</sZ>
</inist:fA14>
<country>Hong Kong</country>
<wicri:noRegion>Pokfulam</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Ying Chen" sort="Ying Chen" uniqKey="Ying Chen" last="Ying Chen">YING CHEN</name>
<affiliation wicri:level="1"><inist:fA14 i1="01"><s1>Department of Microbiology, University of Hong Kong</s1>
<s2>Pokfulam</s2>
<s3>HKG</s3>
<sZ>1 aut.</sZ>
<sZ>2 aut.</sZ>
<sZ>5 aut.</sZ>
<sZ>6 aut.</sZ>
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<sZ>8 aut.</sZ>
<sZ>9 aut.</sZ>
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<country>Hong Kong</country>
<wicri:noRegion>Pokfulam</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Linyu Lu" sort="Linyu Lu" uniqKey="Linyu Lu" last="Linyu Lu">LINYU LU</name>
<affiliation wicri:level="1"><inist:fA14 i1="05"><s1>Department of Biochemistry, University of Hong Kong</s1>
<s2>Pokfulam</s2>
<s3>HKG</s3>
<sZ>10 aut.</sZ>
<sZ>11 aut.</sZ>
<sZ>12 aut.</sZ>
<sZ>19 aut.</sZ>
</inist:fA14>
<country>Hong Kong</country>
<wicri:noRegion>Pokfulam</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Tanner, Julian A" sort="Tanner, Julian A" uniqKey="Tanner J" first="Julian A" last="Tanner">Julian A. Tanner</name>
<affiliation wicri:level="1"><inist:fA14 i1="05"><s1>Department of Biochemistry, University of Hong Kong</s1>
<s2>Pokfulam</s2>
<s3>HKG</s3>
<sZ>10 aut.</sZ>
<sZ>11 aut.</sZ>
<sZ>12 aut.</sZ>
<sZ>19 aut.</sZ>
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<country>Hong Kong</country>
<wicri:noRegion>Pokfulam</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Watt, Rory M" sort="Watt, Rory M" uniqKey="Watt R" first="Rory M." last="Watt">Rory M. Watt</name>
<affiliation wicri:level="1"><inist:fA14 i1="04"><s1>Department of Chemistry and Open Laboratory of Chemical Biology, University of Hong Kong</s1>
<s2>Pokfulam</s2>
<s3>HKG</s3>
<sZ>4 aut.</sZ>
<sZ>12 aut.</sZ>
</inist:fA14>
<country>Hong Kong</country>
<wicri:noRegion>Pokfulam</wicri:noRegion>
</affiliation>
<affiliation wicri:level="1"><inist:fA14 i1="05"><s1>Department of Biochemistry, University of Hong Kong</s1>
<s2>Pokfulam</s2>
<s3>HKG</s3>
<sZ>10 aut.</sZ>
<sZ>11 aut.</sZ>
<sZ>12 aut.</sZ>
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</inist:fA14>
<country>Hong Kong</country>
<wicri:noRegion>Pokfulam</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Niccolai, Neri" sort="Niccolai, Neri" uniqKey="Niccolai N" first="Neri" last="Niccolai">Neri Niccolai</name>
<affiliation wicri:level="1"><inist:fA14 i1="06"><s1>Biomolecular Structure Research Centre, University of Siena</s1>
<s2>Siena</s2>
<s3>ITA</s3>
<sZ>13 aut.</sZ>
<sZ>14 aut.</sZ>
<sZ>15 aut.</sZ>
</inist:fA14>
<country>Italie</country>
<wicri:noRegion>Siena</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Bernini, Andrea" sort="Bernini, Andrea" uniqKey="Bernini A" first="Andrea" last="Bernini">Andrea Bernini</name>
<affiliation wicri:level="1"><inist:fA14 i1="06"><s1>Biomolecular Structure Research Centre, University of Siena</s1>
<s2>Siena</s2>
<s3>ITA</s3>
<sZ>13 aut.</sZ>
<sZ>14 aut.</sZ>
<sZ>15 aut.</sZ>
</inist:fA14>
<country>Italie</country>
<wicri:noRegion>Siena</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Spiga, Ottavia" sort="Spiga, Ottavia" uniqKey="Spiga O" first="Ottavia" last="Spiga">Ottavia Spiga</name>
<affiliation wicri:level="1"><inist:fA14 i1="06"><s1>Biomolecular Structure Research Centre, University of Siena</s1>
<s2>Siena</s2>
<s3>ITA</s3>
<sZ>13 aut.</sZ>
<sZ>14 aut.</sZ>
<sZ>15 aut.</sZ>
</inist:fA14>
<country>Italie</country>
<wicri:noRegion>Siena</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Woo, Patrick C Y" sort="Woo, Patrick C Y" uniqKey="Woo P" first="Patrick C. Y." last="Woo">Patrick C. Y. Woo</name>
<affiliation wicri:level="1"><inist:fA14 i1="01"><s1>Department of Microbiology, University of Hong Kong</s1>
<s2>Pokfulam</s2>
<s3>HKG</s3>
<sZ>1 aut.</sZ>
<sZ>2 aut.</sZ>
<sZ>5 aut.</sZ>
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<sZ>9 aut.</sZ>
<sZ>16 aut.</sZ>
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</inist:fA14>
<country>Hong Kong</country>
<wicri:noRegion>Pokfulam</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Kung, Hsiang Fu" sort="Kung, Hsiang Fu" uniqKey="Kung H" first="Hsiang-Fu" last="Kung">Hsiang-Fu Kung</name>
<affiliation wicri:level="1"><inist:fA14 i1="02"><s1>Institute of Molecular Biology, University of Hong Kong</s1>
<s2>Pokfulam</s2>
<s3>HKG</s3>
<sZ>3 aut.</sZ>
<sZ>17 aut.</sZ>
</inist:fA14>
<country>Hong Kong</country>
<wicri:noRegion>Pokfulam</wicri:noRegion>
</affiliation>
<affiliation wicri:level="4"><inist:fA14 i1="03"><s1>Centre for Emerging Infectious Diseases, Faculty of Medicine, Chinese University of Hong Kong</s1>
<s3>HKG</s3>
<sZ>3 aut.</sZ>
<sZ>17 aut.</sZ>
</inist:fA14>
<country>Hong Kong</country>
<placeName><settlement type="city">Sha Tin</settlement>
</placeName>
<orgName type="university">Université chinoise de Hong Kong</orgName>
</affiliation>
</author>
<author><name sortKey="Yuen, Kwok Yung" sort="Yuen, Kwok Yung" uniqKey="Yuen K" first="Kwok-Yung" last="Yuen">Kwok-Yung Yuen</name>
<affiliation wicri:level="1"><inist:fA14 i1="01"><s1>Department of Microbiology, University of Hong Kong</s1>
<s2>Pokfulam</s2>
<s3>HKG</s3>
<sZ>1 aut.</sZ>
<sZ>2 aut.</sZ>
<sZ>5 aut.</sZ>
<sZ>6 aut.</sZ>
<sZ>7 aut.</sZ>
<sZ>8 aut.</sZ>
<sZ>9 aut.</sZ>
<sZ>16 aut.</sZ>
<sZ>18 aut.</sZ>
</inist:fA14>
<country>Hong Kong</country>
<wicri:noRegion>Pokfulam</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Huang, Jian Dong" sort="Huang, Jian Dong" uniqKey="Huang J" first="Jian-Dong" last="Huang">Jian-Dong Huang</name>
<affiliation wicri:level="1"><inist:fA14 i1="05"><s1>Department of Biochemistry, University of Hong Kong</s1>
<s2>Pokfulam</s2>
<s3>HKG</s3>
<sZ>10 aut.</sZ>
<sZ>11 aut.</sZ>
<sZ>12 aut.</sZ>
<sZ>19 aut.</sZ>
</inist:fA14>
<country>Hong Kong</country>
<wicri:noRegion>Pokfulam</wicri:noRegion>
</affiliation>
</author>
</analytic>
<series><title level="j" type="main">Antiviral therapy : (London)</title>
<title level="j" type="abbreviated">Antivir. ther. : (Lond.)</title>
<idno type="ISSN">1359-6535</idno>
<imprint><date when="2005">2005</date>
</imprint>
</series>
</biblStruct>
</sourceDesc>
<seriesStmt><title level="j" type="main">Antiviral therapy : (London)</title>
<title level="j" type="abbreviated">Antivir. ther. : (Lond.)</title>
<idno type="ISSN">1359-6535</idno>
</seriesStmt>
</fileDesc>
<profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Amino Acid Sequence</term>
<term>Animals</term>
<term>Antiviral Agents (chemistry)</term>
<term>Antiviral Agents (pharmacology)</term>
<term>Cell Line</term>
<term>Dose-Response Relationship, Drug</term>
<term>Humans</term>
<term>Membrane Glycoproteins (chemistry)</term>
<term>Molecular Sequence Data</term>
<term>Peptides</term>
<term>Peptides (chemistry)</term>
<term>Peptides (pharmacology)</term>
<term>Protein</term>
<term>Protein Conformation</term>
<term>SARS Virus (drug effects)</term>
<term>Severe acute respiratory syndrome virus</term>
<term>Spike Glycoprotein, Coronavirus</term>
<term>Viral Envelope Proteins (chemistry)</term>
</keywords>
<keywords scheme="KwdFr" xml:lang="fr"><term>Animaux</term>
<term>Antiviraux ()</term>
<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>
</keywords>
<keywords scheme="MESH" type="chemical" qualifier="chemistry" xml:lang="en"><term>Antiviral Agents</term>
<term>Membrane Glycoproteins</term>
<term>Peptides</term>
<term>Viral Envelope Proteins</term>
</keywords>
<keywords scheme="MESH" type="chemical" qualifier="pharmacology" xml:lang="en"><term>Antiviral Agents</term>
<term>Peptides</term>
</keywords>
<keywords scheme="MESH" qualifier="drug effects" xml:lang="en"><term>SARS Virus</term>
</keywords>
<keywords scheme="MESH" qualifier="pharmacologie" xml:lang="fr"><term>Antiviraux</term>
<term>Peptides</term>
</keywords>
<keywords scheme="MESH" xml:lang="en"><term>Amino Acid Sequence</term>
<term>Animals</term>
<term>Cell Line</term>
<term>Dose-Response Relationship, Drug</term>
<term>Humans</term>
<term>Molecular Sequence Data</term>
<term>Protein Conformation</term>
<term>Spike Glycoprotein, Coronavirus</term>
</keywords>
<keywords scheme="Pascal" xml:lang="fr"><term>Animaux</term>
<term>Antiviraux</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>Peptide</term>
<term>Peptides</term>
<term>Protéine</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>
<term>Virus syndrome respiratoire aigu sévère</term>
</keywords>
</textClass>
</profileDesc>
</teiHeader>
<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 10000-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>
</TEI>
<affiliations><list><country><li>Hong Kong</li>
<li>Italie</li>
</country>
<settlement><li>Sha Tin</li>
</settlement>
<orgName><li>Université chinoise de Hong Kong</li>
</orgName>
</list>
<tree><country name="Hong Kong"><noRegion><name sortKey="Zheng, Bo Jian" sort="Zheng, Bo Jian" uniqKey="Zheng B" first="Bo-Jian" last="Zheng">Bo-Jian Zheng</name>
</noRegion>
<name sortKey="He, Ming Liang" sort="He, Ming Liang" uniqKey="He M" first="Ming-Liang" last="He">Ming-Liang He</name>
<name sortKey="He, Ming Liang" sort="He, Ming Liang" uniqKey="He M" first="Ming-Liang" last="He">Ming-Liang He</name>
<name sortKey="Honglin Chen" sort="Honglin Chen" uniqKey="Honglin Chen" last="Honglin Chen">HONGLIN CHEN</name>
<name sortKey="Hongzhe Sun" sort="Hongzhe Sun" uniqKey="Hongzhe Sun" last="Hongzhe Sun">HONGZHE SUN</name>
<name sortKey="Huang, Jian Dong" sort="Huang, Jian Dong" uniqKey="Huang J" first="Jian-Dong" last="Huang">Jian-Dong Huang</name>
<name sortKey="Kung, Hsiang Fu" sort="Kung, Hsiang Fu" uniqKey="Kung H" first="Hsiang-Fu" last="Kung">Hsiang-Fu Kung</name>
<name sortKey="Kung, Hsiang Fu" sort="Kung, Hsiang Fu" uniqKey="Kung H" first="Hsiang-Fu" last="Kung">Hsiang-Fu Kung</name>
<name sortKey="Lanying Du" sort="Lanying Du" uniqKey="Lanying Du" last="Lanying Du">LANYING DU</name>
<name sortKey="Linyu Lu" sort="Linyu Lu" uniqKey="Linyu Lu" last="Linyu Lu">LINYU LU</name>
<name sortKey="Tanner, Julian A" sort="Tanner, Julian A" uniqKey="Tanner J" first="Julian A" last="Tanner">Julian A. Tanner</name>
<name sortKey="Watt, Rory M" sort="Watt, Rory M" uniqKey="Watt R" first="Rory M." last="Watt">Rory M. Watt</name>
<name sortKey="Watt, Rory M" sort="Watt, Rory M" uniqKey="Watt R" first="Rory M." last="Watt">Rory M. Watt</name>
<name sortKey="Wong, Kin Ling" sort="Wong, Kin Ling" uniqKey="Wong K" first="Kin-Ling" last="Wong">Kin-Ling Wong</name>
<name sortKey="Woo, Patrick C Y" sort="Woo, Patrick C Y" uniqKey="Woo P" first="Patrick C. Y." last="Woo">Patrick C. Y. Woo</name>
<name sortKey="Yi Guan" sort="Yi Guan" uniqKey="Yi Guan" last="Yi Guan">YI GUAN</name>
<name sortKey="Ying Chen" sort="Ying Chen" uniqKey="Ying Chen" last="Ying Chen">YING CHEN</name>
<name sortKey="Ying Zheng" sort="Ying Zheng" uniqKey="Ying Zheng" last="Ying Zheng">YING ZHENG</name>
<name sortKey="Yuen, Kwok Yung" sort="Yuen, Kwok Yung" uniqKey="Yuen K" first="Kwok-Yung" last="Yuen">Kwok-Yung Yuen</name>
</country>
<country name="Italie"><noRegion><name sortKey="Niccolai, Neri" sort="Niccolai, Neri" uniqKey="Niccolai N" first="Neri" last="Niccolai">Neri Niccolai</name>
</noRegion>
<name sortKey="Bernini, Andrea" sort="Bernini, Andrea" uniqKey="Bernini A" first="Andrea" last="Bernini">Andrea Bernini</name>
<name sortKey="Spiga, Ottavia" sort="Spiga, Ottavia" uniqKey="Spiga O" first="Ottavia" last="Spiga">Ottavia Spiga</name>
</country>
</tree>
</affiliations>
</record>

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Synthetic peptides outside the spike protein heptad repeat regions as potent inhibitors of SARS-associated coronavirus

Synthetic peptides outside the spike protein heptad repeat regions as potent inhibitors of SARS-associated coronavirus

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