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Receptor and viral determinants of SARS‐coronavirus adaptation to human ACE2

Identifieur interne : 001261 ( Pmc/Checkpoint ); précédent : 001260; suivant : 001262

Receptor and viral determinants of SARS‐coronavirus adaptation to human ACE2

Auteurs : Wenhui Li ; Chengsheng Zhang ; Jianhua Sui ; Jens H. Kuhn ; Michael J. Moore ; Shiwen Luo ; Swee-Kee Wong ; I-Chueh Huang ; Keming Xu ; Natalya Vasilieva ; Akikazu Murakami ; Yaqing He ; Wayne A. Marasco ; Yi Guan ; Hyeryun Choe ; Michael Farzan

Source :

RBID : PMC:1142572

Abstract

Human angiotensin‐converting enzyme 2 (ACE2) is a functional receptor for SARS coronavirus (SARS‐CoV). Here we identify the SARS‐CoV spike (S)‐protein‐binding site on ACE2. We also compare S proteins of SARS‐CoV isolated during the 2002–2003 SARS outbreak and during the much less severe 2003–2004 outbreak, and from palm civets, a possible source of SARS‐CoV found in humans. All three S proteins bound to and utilized palm‐civet ACE2 efficiently, but the latter two S proteins utilized human ACE2 markedly less efficiently than did the S protein obtained during the earlier human outbreak. The lower affinity of these S proteins could be complemented by altering specific residues within the S‐protein‐binding site of human ACE2 to those of civet ACE2, or by altering S‐protein residues 479 and 487 to residues conserved during the 2002–2003 outbreak. Collectively, these data describe molecular interactions important to the adaptation of SARS‐CoV to human cells, and provide insight into the severity of the 2002–2003 SARS epidemic.


Url:
DOI: 10.1038/sj.emboj.7600640
PubMed: 15791205
PubMed Central: 1142572


Affiliations:


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PMC:1142572

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<p>Human angiotensin‐converting enzyme 2 (ACE2) is a functional receptor for SARS coronavirus (SARS‐CoV). Here we identify the SARS‐CoV spike (S)‐protein‐binding site on ACE2. We also compare S proteins of SARS‐CoV isolated during the 2002–2003 SARS outbreak and during the much less severe 2003–2004 outbreak, and from palm civets, a possible source of SARS‐CoV found in humans. All three S proteins bound to and utilized palm‐civet ACE2 efficiently, but the latter two S proteins utilized human ACE2 markedly less efficiently than did the S protein obtained during the earlier human outbreak. The lower affinity of these S proteins could be complemented by altering specific residues within the S‐protein‐binding site of human ACE2 to those of civet ACE2, or by altering S‐protein residues 479 and 487 to residues conserved during the 2002–2003 outbreak. Collectively, these data describe molecular interactions important to the adaptation of SARS‐CoV to human cells, and provide insight into the severity of the 2002–2003 SARS epidemic.</p>
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<alt-title alt-title-type="right-running-head">SARS‐CoV adaptation to human ACE2</alt-title>
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<contrib-group>
<contrib id="embj7600640-cr-0001" contrib-type="author">
<name>
<surname>Li</surname>
<given-names>Wenhui</given-names>
</name>
<xref ref-type="aff" rid="embj7600640-aff-0001">
<sup>1</sup>
</xref>
</contrib>
<contrib id="embj7600640-cr-0002" contrib-type="author">
<name>
<surname>Zhang</surname>
<given-names>Chengsheng</given-names>
</name>
<xref ref-type="aff" rid="embj7600640-aff-0002">
<sup>2</sup>
</xref>
<xref ref-type="aff" rid="embj7600640-aff-0003">
<sup>3</sup>
</xref>
</contrib>
<contrib id="embj7600640-cr-0003" contrib-type="author">
<name>
<surname>Sui</surname>
<given-names>Jianhua</given-names>
</name>
<xref ref-type="aff" rid="embj7600640-aff-0004">
<sup>4</sup>
</xref>
</contrib>
<contrib id="embj7600640-cr-0004" contrib-type="author">
<name>
<surname>Kuhn</surname>
<given-names>Jens H</given-names>
</name>
<xref ref-type="aff" rid="embj7600640-aff-0001">
<sup>1</sup>
</xref>
<xref ref-type="aff" rid="embj7600640-aff-0005">
<sup>5</sup>
</xref>
</contrib>
<contrib id="embj7600640-cr-0005" contrib-type="author">
<name>
<surname>Moore</surname>
<given-names>Michael J</given-names>
</name>
<xref ref-type="aff" rid="embj7600640-aff-0001">
<sup>1</sup>
</xref>
</contrib>
<contrib id="embj7600640-cr-0006" contrib-type="author">
<name>
<surname>Luo</surname>
<given-names>Shiwen</given-names>
</name>
<xref ref-type="aff" rid="embj7600640-aff-0003">
<sup>3</sup>
</xref>
</contrib>
<contrib id="embj7600640-cr-0007" contrib-type="author">
<name>
<surname>Wong</surname>
<given-names>Swee‐Kee</given-names>
</name>
<xref ref-type="aff" rid="embj7600640-aff-0001">
<sup>1</sup>
</xref>
</contrib>
<contrib id="embj7600640-cr-0008" contrib-type="author">
<name>
<surname>Huang</surname>
<given-names>I‐Chueh</given-names>
</name>
<xref ref-type="aff" rid="embj7600640-aff-0001">
<sup>1</sup>
</xref>
</contrib>
<contrib id="embj7600640-cr-0009" contrib-type="author">
<name>
<surname>Xu</surname>
<given-names>Keming</given-names>
</name>
<xref ref-type="aff" rid="embj7600640-aff-0003">
<sup>3</sup>
</xref>
</contrib>
<contrib id="embj7600640-cr-0010" contrib-type="author">
<name>
<surname>Vasilieva</surname>
<given-names>Natalya</given-names>
</name>
<xref ref-type="aff" rid="embj7600640-aff-0006">
<sup>6</sup>
</xref>
</contrib>
<contrib id="embj7600640-cr-0011" contrib-type="author">
<name>
<surname>Murakami</surname>
<given-names>Akikazu</given-names>
</name>
<xref ref-type="aff" rid="embj7600640-aff-0004">
<sup>4</sup>
</xref>
</contrib>
<contrib id="embj7600640-cr-0012" contrib-type="author">
<name>
<surname>He</surname>
<given-names>Yaqing</given-names>
</name>
<xref ref-type="aff" rid="embj7600640-aff-0007">
<sup>7</sup>
</xref>
</contrib>
<contrib id="embj7600640-cr-0013" contrib-type="author">
<name>
<surname>Marasco</surname>
<given-names>Wayne A</given-names>
</name>
<xref ref-type="aff" rid="embj7600640-aff-0004">
<sup>4</sup>
</xref>
</contrib>
<contrib id="embj7600640-cr-0014" contrib-type="author" corresp="yes">
<name>
<surname>Guan</surname>
<given-names>Yi</given-names>
</name>
<xref ref-type="aff" rid="embj7600640-aff-0003">
<sup>3</sup>
</xref>
</contrib>
<contrib id="embj7600640-cr-0015" contrib-type="author" corresp="yes">
<name>
<surname>Choe</surname>
<given-names>Hyeryun</given-names>
</name>
<xref ref-type="aff" rid="embj7600640-aff-0006">
<sup>6</sup>
</xref>
</contrib>
<contrib id="embj7600640-cr-0016" contrib-type="author" corresp="yes">
<name>
<surname>Farzan</surname>
<given-names>Michael</given-names>
</name>
<xref ref-type="aff" rid="embj7600640-aff-0001">
<sup>1</sup>
</xref>
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<aff id="embj7600640-aff-0001">
<label>
<sup>1</sup>
</label>
<institution>Department of Microbiology and Molecular Genetics, Harvard Medical School, New England Primate Research Center</institution>
<city>Southborough</city>
<named-content content-type="country-part">MA</named-content>
<country country="US">USA</country>
</aff>
<aff id="embj7600640-aff-0002">
<label>
<sup>2</sup>
</label>
<institution>Department of Pathology and Molecular Medicine, McMaster University</institution>
<city>Hamilton</city>
<named-content content-type="country-part">Ontario</named-content>
<country country="CA">Canada</country>
</aff>
<aff id="embj7600640-aff-0003">
<label>
<sup>3</sup>
</label>
<institution>Department of Microbiology, Queen Mary Hospital, The University of Hong Kong</institution>
<city>Hong Kong SAR</city>
<country country="HK">PRC</country>
</aff>
<aff id="embj7600640-aff-0004">
<label>
<sup>4</sup>
</label>
<institution>Department of Medicine, Dana‐Farber Cancer Institute, Harvard Medical School</institution>
<city>Boston</city>
<named-content content-type="country-part">MA</named-content>
<country country="US">USA</country>
</aff>
<aff id="embj7600640-aff-0005">
<label>
<sup>5</sup>
</label>
<institution>Department of Biology, Chemistry, Pharmacy, Freie Universität Berlin</institution>
<city>Berlin</city>
<country country="DE">Germany</country>
</aff>
<aff id="embj7600640-aff-0006">
<label>
<sup>6</sup>
</label>
<institution>Department of Pediatrics, Children's Hospital, Harvard Medical School</institution>
<city>Boston</city>
<named-content content-type="country-part">MA</named-content>
<country country="US">USA</country>
</aff>
<aff id="embj7600640-aff-0007">
<label>
<sup>7</sup>
</label>
<institution>Center for Disease Control and Prevention of Shenzhen</institution>
<city>Shenzhen</city>
<named-content content-type="country-part">Guangdong Province</named-content>
<country country="CN">PRC</country>
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<author-notes>
<corresp id="correspondenceTo">
<label>*</label>
Corresponding authors: Department of Microbiology, Queen Mary Hospital, The University of Hong Kong, Hong Kong SAR, PRC. E‐mail:
<email>yguan@hkucc.hku.hk</email>
Department of Pediatrics, Children's Hospital, Harvard Medical School, Boston, MA 02115, USA. E‐mail:
<email>hyeryun.choe@tch.harvard.edu</email>
Department of Microbiology and Molecular Genetics, Harvard Medical School, New England Primate Research Center, Southborough, MA 01772‐9102, USA. Tel.: +1 617 768 8372; Fax: +1 617 768 8738; E‐mail:
<email>farzan@hms.harvard.edu</email>
</corresp>
</author-notes>
<pub-date pub-type="ppub">
<day>20</day>
<month>4</month>
<year>2005</year>
</pub-date>
<pub-date pub-type="epub">
<day>24</day>
<month>3</month>
<year>2005</year>
</pub-date>
<volume>24</volume>
<issue>8</issue>
<issue-id pub-id-type="doi">10.1002/emboj.v24.8</issue-id>
<fpage>1634</fpage>
<lpage>1643</lpage>
<history>
<date date-type="received">
<day>09</day>
<month>12</month>
<year>2004</year>
</date>
<date date-type="accepted">
<day>04</day>
<month>3</month>
<year>2005</year>
</date>
</history>
<permissions>
<pmc-comment> Copyright © 2013 Wiley Periodicals, Inc </pmc-comment>
<copyright-statement content-type="article-copyright">Copyright © 2005 European Molecular Biology Organization</copyright-statement>
<license>
<license-p>This article is being made freely available through PubMed Central as part of the COVID-19 public health emergency response. It can be used for unrestricted research re-use and analysis in any form or by any means with acknowledgement of the original source, for the duration of the public health emergency.</license-p>
</license>
</permissions>
<self-uri content-type="pdf" xlink:href="file:EMBJ-24-1634.pdf"></self-uri>
<abstract>
<p>Human angiotensin‐converting enzyme 2 (ACE2) is a functional receptor for SARS coronavirus (SARS‐CoV). Here we identify the SARS‐CoV spike (S)‐protein‐binding site on ACE2. We also compare S proteins of SARS‐CoV isolated during the 2002–2003 SARS outbreak and during the much less severe 2003–2004 outbreak, and from palm civets, a possible source of SARS‐CoV found in humans. All three S proteins bound to and utilized palm‐civet ACE2 efficiently, but the latter two S proteins utilized human ACE2 markedly less efficiently than did the S protein obtained during the earlier human outbreak. The lower affinity of these S proteins could be complemented by altering specific residues within the S‐protein‐binding site of human ACE2 to those of civet ACE2, or by altering S‐protein residues 479 and 487 to residues conserved during the 2002–2003 outbreak. Collectively, these data describe molecular interactions important to the adaptation of SARS‐CoV to human cells, and provide insight into the severity of the 2002–2003 SARS epidemic.</p>
</abstract>
<kwd-group kwd-group-type="author-generated">
<kwd id="embj7600640-kwd-0001">angiotensin‐converting enzyme 2</kwd>
<kwd id="embj7600640-kwd-0002">coronavirus</kwd>
<kwd id="embj7600640-kwd-0003">severe acute respiratory syndrome</kwd>
<kwd id="embj7600640-kwd-0004">viral adaptation</kwd>
</kwd-group>
<kwd-group kwd-group-type="subject-categories">
<title>Subject Categories</title>
<kwd>Microbiology, Virology & Host Pathogen Interaction</kwd>
<kwd>Molecular Biology of Disease</kwd>
</kwd-group>
<counts>
<page-count count="10"></page-count>
</counts>
<custom-meta-group>
<custom-meta>
<meta-name>source-schema-version-number</meta-name>
<meta-value>2.0</meta-value>
</custom-meta>
<custom-meta>
<meta-name>cover-date</meta-name>
<meta-value>April 20, 2005</meta-value>
</custom-meta>
<custom-meta>
<meta-name>details-of-publishers-convertor</meta-name>
<meta-value>Converter:WILEY_ML3GV2_TO_JATSPMC version:5.8.0 mode:remove_FC converted:15.04.2020</meta-value>
</custom-meta>
</custom-meta-group>
</article-meta>
</front>
</pmc>
<affiliations>
<list></list>
<tree>
<noCountry>
<name sortKey="Choe, Hyeryun" sort="Choe, Hyeryun" uniqKey="Choe H" first="Hyeryun" last="Choe">Hyeryun Choe</name>
<name sortKey="Farzan, Michael" sort="Farzan, Michael" uniqKey="Farzan M" first="Michael" last="Farzan">Michael Farzan</name>
<name sortKey="Guan, Yi" sort="Guan, Yi" uniqKey="Guan Y" first="Yi" last="Guan">Yi Guan</name>
<name sortKey="He, Yaqing" sort="He, Yaqing" uniqKey="He Y" first="Yaqing" last="He">Yaqing He</name>
<name sortKey="Huang, I Hueh" sort="Huang, I Hueh" uniqKey="Huang I" first="I-Chueh" last="Huang">I-Chueh Huang</name>
<name sortKey="Kuhn, Jens H" sort="Kuhn, Jens H" uniqKey="Kuhn J" first="Jens H" last="Kuhn">Jens H. Kuhn</name>
<name sortKey="Li, Wenhui" sort="Li, Wenhui" uniqKey="Li W" first="Wenhui" last="Li">Wenhui Li</name>
<name sortKey="Luo, Shiwen" sort="Luo, Shiwen" uniqKey="Luo S" first="Shiwen" last="Luo">Shiwen Luo</name>
<name sortKey="Marasco, Wayne A" sort="Marasco, Wayne A" uniqKey="Marasco W" first="Wayne A" last="Marasco">Wayne A. Marasco</name>
<name sortKey="Moore, Michael J" sort="Moore, Michael J" uniqKey="Moore M" first="Michael J" last="Moore">Michael J. Moore</name>
<name sortKey="Murakami, Akikazu" sort="Murakami, Akikazu" uniqKey="Murakami A" first="Akikazu" last="Murakami">Akikazu Murakami</name>
<name sortKey="Sui, Jianhua" sort="Sui, Jianhua" uniqKey="Sui J" first="Jianhua" last="Sui">Jianhua Sui</name>
<name sortKey="Vasilieva, Natalya" sort="Vasilieva, Natalya" uniqKey="Vasilieva N" first="Natalya" last="Vasilieva">Natalya Vasilieva</name>
<name sortKey="Wong, Swee Ee" sort="Wong, Swee Ee" uniqKey="Wong S" first="Swee-Kee" last="Wong">Swee-Kee Wong</name>
<name sortKey="Xu, Keming" sort="Xu, Keming" uniqKey="Xu K" first="Keming" last="Xu">Keming Xu</name>
<name sortKey="Zhang, Chengsheng" sort="Zhang, Chengsheng" uniqKey="Zhang C" first="Chengsheng" last="Zhang">Chengsheng Zhang</name>
</noCountry>
</tree>
</affiliations>
</record>

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