Synthetic peptides outside the spike protein heptad repeat regions as potent inhibitors of SARS-associated coronavirus
Identifieur interne : 000318 ( PascalFrancis/Curation ); précédent : 000317; suivant : 000319Synthetic 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.
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- Pascal (Inist)
English descriptors
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.
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<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en" level="a">Synthetic peptides outside the spike protein heptad repeat regions as potent inhibitors of SARS-associated coronavirus</title><author><name sortKey="Zheng, Bo Jian" sort="Zheng, Bo Jian" uniqKey="Zheng B" first="Bo-Jian" last="Zheng">Bo-Jian Zheng</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></affiliation></author><author><name sortKey="Yi Guan" sort="Yi Guan" uniqKey="Yi Guan" last="Yi Guan">YI GUAN</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></affiliation></author><author><name sortKey="He, Ming Liang" sort="He, Ming Liang" uniqKey="He M" first="Ming-Liang" last="He">Ming-Liang He</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></affiliation><affiliation wicri:level="1"><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></affiliation></author><author><name sortKey="Hongzhe Sun" sort="Hongzhe Sun" uniqKey="Hongzhe Sun" last="Hongzhe Sun">HONGZHE SUN</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></affiliation></author><author><name sortKey="Lanying Du" sort="Lanying Du" uniqKey="Lanying Du" last="Lanying Du">LANYING DU</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></affiliation></author><author><name sortKey="Ying Zheng" sort="Ying Zheng" uniqKey="Ying Zheng" last="Ying Zheng">YING ZHENG</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></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><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></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></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><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></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></affiliation></author><author><name sortKey="Tanner, Julian A" sort="Tanner, Julian A" uniqKey="Tanner J" first="Julian A" last="Tanner">Julian A. 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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></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><sZ>19 aut.</sZ></inist:fA14><country>Hong Kong</country></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></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></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></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><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></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></affiliation><affiliation wicri:level="1"><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></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></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></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">INIST</idno><idno type="inist">05-0250654</idno><date when="2005">2005</date><idno type="stanalyst">PASCAL 05-0250654 INIST</idno><idno type="RBID">Pascal:05-0250654</idno><idno type="wicri:Area/PascalFrancis/Corpus">000672</idno><idno type="wicri:Area/PascalFrancis/Curation">000318</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en" level="a">Synthetic peptides outside the spike protein heptad repeat regions as potent inhibitors of SARS-associated coronavirus</title><author><name sortKey="Zheng, Bo Jian" sort="Zheng, Bo Jian" uniqKey="Zheng B" first="Bo-Jian" last="Zheng">Bo-Jian Zheng</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></affiliation></author><author><name sortKey="Yi Guan" sort="Yi Guan" uniqKey="Yi Guan" last="Yi Guan">YI GUAN</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></affiliation></author><author><name sortKey="He, Ming Liang" sort="He, Ming Liang" uniqKey="He M" first="Ming-Liang" last="He">Ming-Liang He</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></affiliation><affiliation wicri:level="1"><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></affiliation></author><author><name sortKey="Hongzhe Sun" sort="Hongzhe Sun" uniqKey="Hongzhe Sun" last="Hongzhe Sun">HONGZHE SUN</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></affiliation></author><author><name sortKey="Lanying Du" sort="Lanying Du" uniqKey="Lanying Du" last="Lanying Du">LANYING DU</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></affiliation></author><author><name sortKey="Ying Zheng" sort="Ying Zheng" uniqKey="Ying Zheng" last="Ying Zheng">YING ZHENG</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></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><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></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></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><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></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></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></inist:fA14><country>Hong Kong</country></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></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><sZ>19 aut.</sZ></inist:fA14><country>Hong Kong</country></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></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></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></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><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></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></affiliation><affiliation wicri:level="1"><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></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></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></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>Peptides</term><term>Protein</term><term>Severe acute respiratory syndrome virus</term></keywords><keywords scheme="Pascal" xml:lang="fr"><term>Peptide</term><term>Protéine</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><inist><standard h6="B"><pA><fA01 i1="01" i2="1"><s0>1359-6535</s0></fA01><fA03 i2="1"><s0>Antivir. ther. : (Lond.)</s0></fA03><fA05><s2>10</s2></fA05><fA06><s2>3</s2></fA06><fA08 i1="01" i2="1" l="ENG"><s1>Synthetic peptides outside the spike protein heptad repeat regions as potent inhibitors of SARS-associated coronavirus</s1></fA08><fA11 i1="01" i2="1"><s1>ZHENG (Bo-Jian)</s1></fA11><fA11 i1="02" i2="1"><s1>YI GUAN</s1></fA11><fA11 i1="03" i2="1"><s1>HE (Ming-Liang)</s1></fA11><fA11 i1="04" i2="1"><s1>HONGZHE SUN</s1></fA11><fA11 i1="05" i2="1"><s1>LANYING DU</s1></fA11><fA11 i1="06" i2="1"><s1>YING ZHENG</s1></fA11><fA11 i1="07" i2="1"><s1>WONG (Kin-Ling)</s1></fA11><fA11 i1="08" i2="1"><s1>HONGLIN CHEN</s1></fA11><fA11 i1="09" i2="1"><s1>YING CHEN</s1></fA11><fA11 i1="10" i2="1"><s1>LINYU LU</s1></fA11><fA11 i1="11" i2="1"><s1>TANNER (Julian A)</s1></fA11><fA11 i1="12" i2="1"><s1>WATT (Rory M.)</s1></fA11><fA11 i1="13" i2="1"><s1>NICCOLAI (Neri)</s1></fA11><fA11 i1="14" i2="1"><s1>BERNINI (Andrea)</s1></fA11><fA11 i1="15" i2="1"><s1>SPIGA (Ottavia)</s1></fA11><fA11 i1="16" i2="1"><s1>WOO (Patrick C. Y.)</s1></fA11><fA11 i1="17" i2="1"><s1>KUNG (Hsiang-Fu)</s1></fA11><fA11 i1="18" i2="1"><s1>YUEN (Kwok-Yung)</s1></fA11><fA11 i1="19" i2="1"><s1>HUANG (Jian-Dong)</s1></fA11><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></fA14><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></fA14><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></fA14><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></fA14><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></fA14><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></fA14><fA20><s1>393-403</s1></fA20><fA21><s1>2005</s1></fA21><fA23 i1="01"><s0>ENG</s0></fA23><fA43 i1="01"><s1>INIST</s1><s2>27047</s2><s5>354000125439640030</s5></fA43><fA44><s0>0000</s0><s1>© 2005 INIST-CNRS. All rights reserved.</s1></fA44><fA45><s0>39 ref.</s0></fA45><fA47 i1="01" i2="1"><s0>05-0250654</s0></fA47><fA60><s1>P</s1></fA60><fA61><s0>A</s0></fA61><fA64 i1="01" i2="1"><s0>Antiviral therapy : (London)</s0></fA64><fA66 i1="01"><s0>GBR</s0></fA66><fC01 i1="01" l="ENG"><s0>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.</s0></fC01><fC02 i1="01" i2="X"><s0>002B02S05</s0></fC02><fC03 i1="01" i2="X" l="FRE"><s0>Peptide</s0><s5>01</s5></fC03><fC03 i1="01" i2="X" l="ENG"><s0>Peptides</s0><s5>01</s5></fC03><fC03 i1="01" i2="X" l="SPA"><s0>Péptido</s0><s5>01</s5></fC03><fC03 i1="02" i2="X" l="FRE"><s0>Protéine</s0><s5>02</s5></fC03><fC03 i1="02" i2="X" l="ENG"><s0>Protein</s0><s5>02</s5></fC03><fC03 i1="02" i2="X" l="SPA"><s0>Proteína</s0><s5>02</s5></fC03><fC03 i1="03" i2="X" l="FRE"><s0>Virus syndrome respiratoire aigu sévère</s0><s2>NW</s2><s5>03</s5></fC03><fC03 i1="03" i2="X" l="ENG"><s0>Severe acute respiratory syndrome virus</s0><s2>NW</s2><s5>03</s5></fC03><fC03 i1="03" i2="X" l="SPA"><s0>Severe acute respiratory syndrome virus</s0><s2>NW</s2><s5>03</s5></fC03><fC07 i1="01" i2="X" l="FRE"><s0>Coronavirus</s0><s2>NW</s2></fC07><fC07 i1="01" i2="X" l="ENG"><s0>Coronavirus</s0><s2>NW</s2></fC07><fC07 i1="01" i2="X" l="SPA"><s0>Coronavirus</s0><s2>NW</s2></fC07><fC07 i1="02" i2="X" l="FRE"><s0>Coronaviridae</s0><s2>NW</s2></fC07><fC07 i1="02" i2="X" l="ENG"><s0>Coronaviridae</s0><s2>NW</s2></fC07><fC07 i1="02" i2="X" l="SPA"><s0>Coronaviridae</s0><s2>NW</s2></fC07><fC07 i1="03" i2="X" l="FRE"><s0>Nidovirales</s0><s2>NW</s2></fC07><fC07 i1="03" i2="X" l="ENG"><s0>Nidovirales</s0><s2>NW</s2></fC07><fC07 i1="03" i2="X" l="SPA"><s0>Nidovirales</s0><s2>NW</s2></fC07><fC07 i1="04" i2="X" l="FRE"><s0>Virus</s0><s2>NW</s2></fC07><fC07 i1="04" i2="X" l="ENG"><s0>Virus</s0><s2>NW</s2></fC07><fC07 i1="04" i2="X" l="SPA"><s0>Virus</s0><s2>NW</s2></fC07><fN21><s1>171</s1></fN21><fN44 i1="01"><s1>OTO</s1></fN44><fN82><s1>OTO</s1></fN82></pA></standard></inist></record>Pour manipuler ce document sous Unix (Dilib)
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