Synthetic peptides outside the spike protein heptad repeat regions as potent inhibitors of SARS-associated coronavirus.
Identifieur interne : 002715 ( PubMed/Corpus ); précédent : 002714; suivant : 002716Synthetic peptides outside the spike protein heptad repeat regions as potent inhibitors of SARS-associated coronavirus.
Auteurs : Bo-Jion Zheng ; 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.
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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Tanner</name></author><author><name sortKey="Watt, Rory M" sort="Watt, Rory M" uniqKey="Watt R" first="Rory M" last="Watt">Rory M. Watt</name></author><author><name sortKey="Niccolai, Neri" sort="Niccolai, Neri" uniqKey="Niccolai N" first="Neri" last="Niccolai">Neri Niccolai</name></author><author><name sortKey="Bernini, Andrea" sort="Bernini, Andrea" uniqKey="Bernini A" first="Andrea" last="Bernini">Andrea Bernini</name></author><author><name sortKey="Spiga, Ottavia" sort="Spiga, Ottavia" uniqKey="Spiga O" first="Ottavia" last="Spiga">Ottavia Spiga</name></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></author><author><name sortKey="Kung, Hsiang Fu" sort="Kung, Hsiang Fu" uniqKey="Kung H" first="Hsiang-Fu" last="Kung">Hsiang-Fu Kung</name></author><author><name sortKey="Yuen, Kwok Yung" sort="Yuen, Kwok Yung" uniqKey="Yuen K" first="Kwok-Yung" last="Yuen">Kwok-Yung Yuen</name></author><author><name sortKey="Huang, Jian Dong" sort="Huang, Jian Dong" uniqKey="Huang J" first="Jian-Dong" last="Huang">Jian-Dong Huang</name></author></titleStmt><publicationStmt><idno type="wicri:source">PubMed</idno><date when="2005">2005</date><idno type="RBID">pubmed:15918330</idno><idno type="pmid">15918330</idno><idno type="wicri:Area/PubMed/Corpus">002715</idno><idno type="wicri:explorRef" wicri:stream="PubMed" wicri:step="Corpus" wicri:corpus="PubMed">002715</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en">Synthetic peptides outside the spike protein heptad repeat regions as potent inhibitors of SARS-associated coronavirus.</title><author><name sortKey="Zheng, Bo Jion" sort="Zheng, Bo Jion" uniqKey="Zheng B" first="Bo-Jion" last="Zheng">Bo-Jion Zheng</name><affiliation><nlm:affiliation>Department of Microbiology, University of Hong Kong, Pokfulam, Hong Kong SAR, China. bzheng@hkucc.hku.hk</nlm:affiliation></affiliation></author><author><name sortKey="Guan, Yi" sort="Guan, Yi" uniqKey="Guan Y" first="Yi" last="Guan">Yi Guan</name></author><author><name sortKey="Hez, Ming Liang" sort="Hez, Ming Liang" uniqKey="Hez M" first="Ming-Liang" last="Hez">Ming-Liang Hez</name></author><author><name sortKey="Sun, Hongzhe" sort="Sun, Hongzhe" uniqKey="Sun H" first="Hongzhe" last="Sun">Hongzhe Sun</name></author><author><name sortKey="Du, Lanying" sort="Du, Lanying" uniqKey="Du L" first="Lanying" last="Du">Lanying Du</name></author><author><name sortKey="Zheng, Ying" sort="Zheng, Ying" uniqKey="Zheng Y" first="Ying" last="Zheng">Ying Zheng</name></author><author><name sortKey="Wong, Kin Ling" sort="Wong, Kin Ling" uniqKey="Wong K" first="Kin-Ling" last="Wong">Kin-Ling Wong</name></author><author><name sortKey="Chen, Honglin" sort="Chen, Honglin" uniqKey="Chen H" first="Honglin" last="Chen">Honglin Chen</name></author><author><name sortKey="Chen, Ying" sort="Chen, Ying" uniqKey="Chen Y" first="Ying" last="Chen">Ying Chen</name></author><author><name sortKey="Lu, Linyu" sort="Lu, Linyu" uniqKey="Lu L" first="Linyu" last="Lu">Linyu Lu</name></author><author><name sortKey="Tanner, Julian A" sort="Tanner, Julian A" uniqKey="Tanner J" first="Julian A" last="Tanner">Julian A. Tanner</name></author><author><name sortKey="Watt, Rory M" sort="Watt, Rory M" uniqKey="Watt R" first="Rory M" last="Watt">Rory M. Watt</name></author><author><name sortKey="Niccolai, Neri" sort="Niccolai, Neri" uniqKey="Niccolai N" first="Neri" last="Niccolai">Neri Niccolai</name></author><author><name sortKey="Bernini, Andrea" sort="Bernini, Andrea" uniqKey="Bernini A" first="Andrea" last="Bernini">Andrea Bernini</name></author><author><name sortKey="Spiga, Ottavia" sort="Spiga, Ottavia" uniqKey="Spiga O" first="Ottavia" last="Spiga">Ottavia Spiga</name></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></author><author><name sortKey="Kung, Hsiang Fu" sort="Kung, Hsiang Fu" uniqKey="Kung H" first="Hsiang-Fu" last="Kung">Hsiang-Fu Kung</name></author><author><name sortKey="Yuen, Kwok Yung" sort="Yuen, Kwok Yung" uniqKey="Yuen K" first="Kwok-Yung" last="Yuen">Kwok-Yung Yuen</name></author><author><name sortKey="Huang, Jian Dong" sort="Huang, Jian Dong" uniqKey="Huang J" first="Jian-Dong" last="Huang">Jian-Dong Huang</name></author></analytic><series><title level="j">Antiviral therapy</title><idno type="ISSN">1359-6535</idno><imprint><date when="2005" type="published">2005</date></imprint></series></biblStruct></sourceDesc></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 (chemistry)</term><term>Peptides (pharmacology)</term><term>Protein Conformation</term><term>SARS Virus (drug effects)</term><term>Spike Glycoprotein, Coronavirus</term><term>Viral Envelope Proteins (chemistry)</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" 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></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 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></TEI><pubmed><MedlineCitation Status="MEDLINE" Owner="NLM"><PMID Version="1">15918330</PMID><DateCompleted><Year>2005</Year><Month>06</Month><Day>22</Day></DateCompleted><DateRevised><Year>2020</Year><Month>04</Month><Day>15</Day></DateRevised><Article PubModel="Print"><Journal><ISSN IssnType="Print">1359-6535</ISSN><JournalIssue CitedMedium="Print"><Volume>10</Volume><Issue>3</Issue><PubDate><Year>2005</Year></PubDate></JournalIssue><Title>Antiviral therapy</Title><ISOAbbreviation>Antivir. Ther. (Lond.)</ISOAbbreviation></Journal><ArticleTitle>Synthetic peptides outside the spike protein heptad repeat regions as potent inhibitors of SARS-associated coronavirus.</ArticleTitle><Pagination><MedlinePgn>393-403</MedlinePgn></Pagination><Abstract><AbstractText>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.</AbstractText></Abstract><AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Zheng</LastName><ForeName>Bo-Jion</ForeName><Initials>BJ</Initials><AffiliationInfo><Affiliation>Department of Microbiology, University of Hong Kong, Pokfulam, Hong Kong SAR, China. bzheng@hkucc.hku.hk</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Guan</LastName><ForeName>Yi</ForeName><Initials>Y</Initials></Author><Author ValidYN="Y"><LastName>Hez</LastName><ForeName>Ming-Liang</ForeName><Initials>ML</Initials></Author><Author ValidYN="Y"><LastName>Sun</LastName><ForeName>Hongzhe</ForeName><Initials>H</Initials></Author><Author ValidYN="Y"><LastName>Du</LastName><ForeName>Lanying</ForeName><Initials>L</Initials></Author><Author ValidYN="Y"><LastName>Zheng</LastName><ForeName>Ying</ForeName><Initials>Y</Initials></Author><Author ValidYN="Y"><LastName>Wong</LastName><ForeName>Kin-Ling</ForeName><Initials>KL</Initials></Author><Author ValidYN="Y"><LastName>Chen</LastName><ForeName>Honglin</ForeName><Initials>H</Initials></Author><Author ValidYN="Y"><LastName>Chen</LastName><ForeName>Ying</ForeName><Initials>Y</Initials></Author><Author ValidYN="Y"><LastName>Lu</LastName><ForeName>Linyu</ForeName><Initials>L</Initials></Author><Author ValidYN="Y"><LastName>Tanner</LastName><ForeName>Julian A</ForeName><Initials>JA</Initials></Author><Author ValidYN="Y"><LastName>Watt</LastName><ForeName>Rory M</ForeName><Initials>RM</Initials></Author><Author ValidYN="Y"><LastName>Niccolai</LastName><ForeName>Neri</ForeName><Initials>N</Initials></Author><Author ValidYN="Y"><LastName>Bernini</LastName><ForeName>Andrea</ForeName><Initials>A</Initials></Author><Author ValidYN="Y"><LastName>Spiga</LastName><ForeName>Ottavia</ForeName><Initials>O</Initials></Author><Author ValidYN="Y"><LastName>Woo</LastName><ForeName>Patrick C Y</ForeName><Initials>PC</Initials></Author><Author ValidYN="Y"><LastName>Kung</LastName><ForeName>Hsiang-fu</ForeName><Initials>HF</Initials></Author><Author ValidYN="Y"><LastName>Yuen</LastName><ForeName>Kwok-Yung</ForeName><Initials>KY</Initials></Author><Author ValidYN="Y"><LastName>Huang</LastName><ForeName>Jian-Dong</ForeName><Initials>JD</Initials></Author></AuthorList><Language>eng</Language><PublicationTypeList><PublicationType UI="D016428">Journal Article</PublicationType><PublicationType UI="D013485">Research Support, Non-U.S. Gov't</PublicationType></PublicationTypeList></Article><MedlineJournalInfo><Country>England</Country><MedlineTA>Antivir Ther</MedlineTA><NlmUniqueID>9815705</NlmUniqueID><ISSNLinking>1359-6535</ISSNLinking></MedlineJournalInfo><ChemicalList><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D000998">Antiviral Agents</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="C578553">MHV surface projection glycoprotein</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D008562">Membrane Glycoproteins</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D010455">Peptides</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D064370">Spike Glycoprotein, Coronavirus</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D014759">Viral Envelope Proteins</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="C578557">spike glycoprotein, SARS-CoV</NameOfSubstance></Chemical></ChemicalList><CitationSubset>IM</CitationSubset><MeshHeadingList><MeshHeading><DescriptorName UI="D000595" MajorTopicYN="N">Amino Acid Sequence</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D000818" MajorTopicYN="N">Animals</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D000998" MajorTopicYN="N">Antiviral Agents</DescriptorName><QualifierName UI="Q000737" MajorTopicYN="Y">chemistry</QualifierName><QualifierName UI="Q000494" MajorTopicYN="Y">pharmacology</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D002460" MajorTopicYN="N">Cell Line</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D004305" MajorTopicYN="N">Dose-Response Relationship, Drug</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D006801" MajorTopicYN="N">Humans</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D008562" MajorTopicYN="N">Membrane Glycoproteins</DescriptorName><QualifierName UI="Q000737" MajorTopicYN="Y">chemistry</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D008969" MajorTopicYN="N">Molecular Sequence Data</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D010455" MajorTopicYN="N">Peptides</DescriptorName><QualifierName UI="Q000737" MajorTopicYN="Y">chemistry</QualifierName><QualifierName UI="Q000494" MajorTopicYN="Y">pharmacology</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D011487" MajorTopicYN="N">Protein Conformation</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D045473" MajorTopicYN="N">SARS Virus</DescriptorName><QualifierName UI="Q000187" MajorTopicYN="Y">drug effects</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D064370" MajorTopicYN="N">Spike Glycoprotein, Coronavirus</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D014759" MajorTopicYN="N">Viral Envelope Proteins</DescriptorName><QualifierName UI="Q000737" MajorTopicYN="Y">chemistry</QualifierName></MeshHeading></MeshHeadingList></MedlineCitation><PubmedData><History><PubMedPubDate PubStatus="pubmed"><Year>2005</Year><Month>5</Month><Day>28</Day><Hour>9</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="medline"><Year>2005</Year><Month>6</Month><Day>23</Day><Hour>9</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="entrez"><Year>2005</Year><Month>5</Month><Day>28</Day><Hour>9</Hour><Minute>0</Minute></PubMedPubDate></History><PublicationStatus>ppublish</PublicationStatus><ArticleIdList><ArticleId IdType="pubmed">15918330</ArticleId></ArticleIdList></PubmedData></pubmed></record>Pour manipuler ce document sous Unix (Dilib)
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