H2N2V1, France, Analysis, bibRecord, 000193

Novel sialic acid derivatives lock open the 150-loop of an influenza A virus group-1 sialidase.

Identifieur interne : 000193 ( France/Analysis ); précédent : 000192; suivant : 000194

Novel sialic acid derivatives lock open the 150-loop of an influenza A virus group-1 sialidase.

Auteurs : Santosh Rudrawar [Australie] ; Jeffrey C. Dyason [Australie] ; Marie-Anne Rameix-Welti [France] ; Faith J. Rose [Australie] ; Philip S. Kerry [Royaume-Uni] ; Rupert J M. Russell [Royaume-Uni] ; Sylvie Van Der Werf [France] ; Robin J. Thomson [Australie] ; Nadia Naffakh [France] ; Mark Von Itzstein [Australie]

Source :

Nature Communications [ 2041-1723 ] ; 2010-11.

RBID : Hal:pasteur-00546706

Abstract

Influenza virus sialidase has an essential role in the virus' life cycle. Two distinct groups of influenza A virus sialidases have been established, that differ in the flexibility of the '150-loop', providing a more open active site in the apo form of the group-1 compared to group-2 enzymes. In this study we show, through a multidisciplinary approach, that novel sialic acid-based derivatives can exploit this structural difference and selectively inhibit the activity of group-1 sialidases. We also demonstrate that group-1 sialidases from drug-resistant mutant influenza viruses are sensitive to these designed compounds. Moreover, we have determined, by protein X-ray crystallography, that these inhibitors lock open the group-1 sialidase flexible 150-loop, in agreement with our molecular modelling prediction. This is the first direct proof that compounds may be developed to selectively target the pandemic A/H1N1, avian A/H5N1 and other group-1 sialidase-containing viruses, based on an open 150-loop conformation of the enzyme.

Url:

https://hal-pasteur.archives-ouvertes.fr/pasteur-00546706

DOI: 10.1038/ncomms1114

Affiliations:

Australie, France, Royaume-Uni

Links toward previous steps (curation, corpus...)

to stream Hal, to step Corpus: 000222
to stream Hal, to step Curation: 000222
to stream Hal, to step Checkpoint: 000254
to stream Main, to step Merge: 000D77
to stream Main, to step Curation: 000D71
to stream Main, to step Exploration: 000D71
to stream France, to step Extraction: 000193

Links to Exploration step

Hal:pasteur-00546706

Le document en format XML

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          <orgName type="acronym">CNRS</orgName>
          <date type="start">1939-10-19</date>
          <desc>            <address>              <country key="FR"></country>
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          </desc>
        </org>
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</tutelles>
</hal:affiliation>
<country>France</country>
</affiliation>
</author>
<author><name sortKey="Rose, Faith J" sort="Rose, Faith J" uniqKey="Rose F" first="Faith J" last="Rose">Faith J. Rose</name>
<affiliation wicri:level="1"><hal:affiliation type="department" xml:id="struct-135765" status="VALID">          <orgName>Institute for Glycomics</orgName>
          <desc>            <address>              <addrLine>Gold Coast Campus, Queensland 4222</addrLine>
              <country key="AU"></country>
            </address>
          </desc>
          <listRelation>            <relation active="#struct-82142" type="direct"></relation>
          </listRelation>
        <tutelles><tutelle active="#struct-82142" type="direct"><org type="institution" xml:id="struct-82142" status="VALID">          <orgName>Griffith University [Brisbane]</orgName>
          <desc>            <address>              <addrLine>PO Box 3370South Brisbane QLD 4101</addrLine>
              <country key="AU"></country>
            </address>
            <ref type="url">http://www.griffith.edu.au/</ref>
          </desc>
        </org>
</tutelle>
</tutelles>
</hal:affiliation>
<country>Australie</country>
</affiliation>
</author>
<author><name sortKey="Kerry, Philip S" sort="Kerry, Philip S" uniqKey="Kerry P" first="Philip S" last="Kerry">Philip S. Kerry</name>
<affiliation wicri:level="1"><hal:affiliation type="laboratory" xml:id="struct-135766" status="INCOMING">          <orgName>Interdisciplinary Centre for Human and Avian Influenza Research</orgName>
          <desc>            <address>              <addrLine>North Haugh, St Andrews, Fife KY16 9ST,</addrLine>
              <country key="GB"></country>
            </address>
          </desc>
          <listRelation>            <relation active="#struct-14827" type="direct"></relation>
          </listRelation>
        <tutelles><tutelle active="#struct-14827" type="direct"><org type="institution" xml:id="struct-14827" status="VALID">          <orgName>University of St Andrews [Scotland]</orgName>
          <desc>            <address>              <addrLine>St Andrews KY16 9AJ,  Fife,  Scotland, UK</addrLine>
              <country key="GB"></country>
            </address>
            <ref type="url">http://www.st-andrews.ac.uk/</ref>
          </desc>
        </org>
</tutelle>
</tutelles>
</hal:affiliation>
<country>Royaume-Uni</country>
</affiliation>
</author>
<author><name sortKey="Russell, Rupert J M" sort="Russell, Rupert J M" uniqKey="Russell R" first="Rupert J M" last="Russell">Rupert J M. Russell</name>
<affiliation wicri:level="1"><hal:affiliation type="laboratory" xml:id="struct-135766" status="INCOMING">          <orgName>Interdisciplinary Centre for Human and Avian Influenza Research</orgName>
          <desc>            <address>              <addrLine>North Haugh, St Andrews, Fife KY16 9ST,</addrLine>
              <country key="GB"></country>
            </address>
          </desc>
          <listRelation>            <relation active="#struct-14827" type="direct"></relation>
          </listRelation>
        <tutelles><tutelle active="#struct-14827" type="direct"><org type="institution" xml:id="struct-14827" status="VALID">          <orgName>University of St Andrews [Scotland]</orgName>
          <desc>            <address>              <addrLine>St Andrews KY16 9AJ,  Fife,  Scotland, UK</addrLine>
              <country key="GB"></country>
            </address>
            <ref type="url">http://www.st-andrews.ac.uk/</ref>
          </desc>
        </org>
</tutelle>
</tutelles>
</hal:affiliation>
<country>Royaume-Uni</country>
</affiliation>
</author>
<author><name sortKey="Van Der Werf, Sylvie" sort="Van Der Werf, Sylvie" uniqKey="Van Der Werf S" first="Sylvie" last="Van Der Werf">Sylvie Van Der Werf</name>
<affiliation wicri:level="1"><hal:affiliation type="laboratory" xml:id="struct-35815" status="OLD">          <orgName>Génétique Moléculaire des Virus Respiratoires</orgName>
          <desc>            <address>              <addrLine>25-28 rue du Docteur Roux, F-75724 Paris Cedex 15</addrLine>
              <country key="FR"></country>
            </address>
          </desc>
          <listRelation>            <relation active="#struct-300027" type="direct"></relation>
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          </listRelation>
        <tutelles><tutelle active="#struct-300027" type="direct"><org type="institution" xml:id="struct-300027" status="VALID">          <idno type="IdRef">027936643</idno>
          <idno type="ISNI">0000 0001 2353 6535</idno>
          <orgName>Institut Pasteur [Paris]</orgName>
          <date type="start">1887-06-04</date>
          <desc>            <address>              <addrLine>25-28, rue du docteur Roux, 75724 Paris cedex 15</addrLine>
              <country key="FR"></country>
            </address>
            <ref type="url">https://www.pasteur.fr</ref>
          </desc>
        </org>
</tutelle>
<tutelle active="#struct-300301" type="direct"><org type="institution" xml:id="struct-300301" status="OLD">          <idno type="ISNI">0000000121514068</idno>
          <idno type="IdRef">027542084</idno>
          <orgName>Université Paris Diderot - Paris 7</orgName>
          <orgName type="acronym">UPD7</orgName>
          <date type="end">2019-12-31</date>
          <desc>            <address>              <addrLine>5 rue Thomas-Mann - 75205 Paris cedex 13</addrLine>
              <country key="FR"></country>
            </address>
            <ref type="url">http://www.univ-paris-diderot.fr</ref>
          </desc>
        </org>
</tutelle>
<tutelle name="URA3015" active="#struct-441569" type="direct"><org type="institution" xml:id="struct-441569" status="VALID">          <idno type="IdRef">02636817X</idno>
          <idno type="ISNI">0000000122597504</idno>
          <orgName>Centre National de la Recherche Scientifique</orgName>
          <orgName type="acronym">CNRS</orgName>
          <date type="start">1939-10-19</date>
          <desc>            <address>              <country key="FR"></country>
            </address>
            <ref type="url">http://www.cnrs.fr/</ref>
          </desc>
        </org>
</tutelle>
</tutelles>
</hal:affiliation>
<country>France</country>
</affiliation>
</author>
<author><name sortKey="Thomson, Robin J" sort="Thomson, Robin J" uniqKey="Thomson R" first="Robin J" last="Thomson">Robin J. Thomson</name>
<affiliation wicri:level="1"><hal:affiliation type="department" xml:id="struct-135765" status="VALID">          <orgName>Institute for Glycomics</orgName>
          <desc>            <address>              <addrLine>Gold Coast Campus, Queensland 4222</addrLine>
              <country key="AU"></country>
            </address>
          </desc>
          <listRelation>            <relation active="#struct-82142" type="direct"></relation>
          </listRelation>
        <tutelles><tutelle active="#struct-82142" type="direct"><org type="institution" xml:id="struct-82142" status="VALID">          <orgName>Griffith University [Brisbane]</orgName>
          <desc>            <address>              <addrLine>PO Box 3370South Brisbane QLD 4101</addrLine>
              <country key="AU"></country>
            </address>
            <ref type="url">http://www.griffith.edu.au/</ref>
          </desc>
        </org>
</tutelle>
</tutelles>
</hal:affiliation>
<country>Australie</country>
</affiliation>
</author>
<author><name sortKey="Naffakh, Nadia" sort="Naffakh, Nadia" uniqKey="Naffakh N" first="Nadia" last="Naffakh">Nadia Naffakh</name>
<affiliation wicri:level="1"><hal:affiliation type="laboratory" xml:id="struct-35815" status="OLD">          <orgName>Génétique Moléculaire des Virus Respiratoires</orgName>
          <desc>            <address>              <addrLine>25-28 rue du Docteur Roux, F-75724 Paris Cedex 15</addrLine>
              <country key="FR"></country>
            </address>
          </desc>
          <listRelation>            <relation active="#struct-300027" type="direct"></relation>
            <relation active="#struct-300301" type="direct"></relation>
            <relation name="URA3015" active="#struct-441569" type="direct"></relation>
          </listRelation>
        <tutelles><tutelle active="#struct-300027" type="direct"><org type="institution" xml:id="struct-300027" status="VALID">          <idno type="IdRef">027936643</idno>
          <idno type="ISNI">0000 0001 2353 6535</idno>
          <orgName>Institut Pasteur [Paris]</orgName>
          <date type="start">1887-06-04</date>
          <desc>            <address>              <addrLine>25-28, rue du docteur Roux, 75724 Paris cedex 15</addrLine>
              <country key="FR"></country>
            </address>
            <ref type="url">https://www.pasteur.fr</ref>
          </desc>
        </org>
</tutelle>
<tutelle active="#struct-300301" type="direct"><org type="institution" xml:id="struct-300301" status="OLD">          <idno type="ISNI">0000000121514068</idno>
          <idno type="IdRef">027542084</idno>
          <orgName>Université Paris Diderot - Paris 7</orgName>
          <orgName type="acronym">UPD7</orgName>
          <date type="end">2019-12-31</date>
          <desc>            <address>              <addrLine>5 rue Thomas-Mann - 75205 Paris cedex 13</addrLine>
              <country key="FR"></country>
            </address>
            <ref type="url">http://www.univ-paris-diderot.fr</ref>
          </desc>
        </org>
</tutelle>
<tutelle name="URA3015" active="#struct-441569" type="direct"><org type="institution" xml:id="struct-441569" status="VALID">          <idno type="IdRef">02636817X</idno>
          <idno type="ISNI">0000000122597504</idno>
          <orgName>Centre National de la Recherche Scientifique</orgName>
          <orgName type="acronym">CNRS</orgName>
          <date type="start">1939-10-19</date>
          <desc>            <address>              <country key="FR"></country>
            </address>
            <ref type="url">http://www.cnrs.fr/</ref>
          </desc>
        </org>
</tutelle>
</tutelles>
</hal:affiliation>
<country>France</country>
</affiliation>
</author>
<author><name sortKey="Von Itzstein, Mark" sort="Von Itzstein, Mark" uniqKey="Von Itzstein M" first="Mark" last="Von Itzstein">Mark Von Itzstein</name>
<affiliation wicri:level="1"><hal:affiliation type="department" xml:id="struct-135765" status="VALID">          <orgName>Institute for Glycomics</orgName>
          <desc>            <address>              <addrLine>Gold Coast Campus, Queensland 4222</addrLine>
              <country key="AU"></country>
            </address>
          </desc>
          <listRelation>            <relation active="#struct-82142" type="direct"></relation>
          </listRelation>
        <tutelles><tutelle active="#struct-82142" type="direct"><org type="institution" xml:id="struct-82142" status="VALID">          <orgName>Griffith University [Brisbane]</orgName>
          <desc>            <address>              <addrLine>PO Box 3370South Brisbane QLD 4101</addrLine>
              <country key="AU"></country>
            </address>
            <ref type="url">http://www.griffith.edu.au/</ref>
          </desc>
        </org>
</tutelle>
</tutelles>
</hal:affiliation>
<country>Australie</country>
</affiliation>
</author>
</analytic>
<idno type="DOI">10.1038/ncomms1114</idno>
<series><title level="j">Nature Communications</title>
<idno type="ISSN">2041-1723</idno>
<imprint><date type="datePub">2010-11</date>
</imprint>
</series>
</biblStruct>
</sourceDesc>
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<profileDesc><textClass></textClass>
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</teiHeader>
<front><div type="abstract" xml:lang="en">              <p>Influenza virus sialidase has an essential role in the virus' life cycle. Two distinct groups of influenza A virus sialidases have been established, that differ in the flexibility of the '150-loop', providing a more open active site in the apo form of the group-1 compared to group-2 enzymes. In this study we show, through a multidisciplinary approach, that novel sialic acid-based derivatives can exploit this structural difference and selectively inhibit the activity of group-1 sialidases. We also demonstrate that group-1 sialidases from drug-resistant mutant influenza viruses are sensitive to these designed compounds. Moreover, we have determined, by protein X-ray crystallography, that these inhibitors lock open the group-1 sialidase flexible 150-loop, in agreement with our molecular modelling prediction. This is the first direct proof that compounds may be developed to selectively target the pandemic A/H1N1, avian A/H5N1 and other group-1 sialidase-containing viruses, based on an open 150-loop conformation of the enzyme.</p>
            </div>
</front>
</TEI>
<affiliations><list><country><li>Australie</li>
<li>France</li>
<li>Royaume-Uni</li>
</country>
</list>
<tree><country name="Australie"><noRegion><name sortKey="Rudrawar, Santosh" sort="Rudrawar, Santosh" uniqKey="Rudrawar S" first="Santosh" last="Rudrawar">Santosh Rudrawar</name>
</noRegion>
<name sortKey="Dyason, Jeffrey C" sort="Dyason, Jeffrey C" uniqKey="Dyason J" first="Jeffrey C" last="Dyason">Jeffrey C. Dyason</name>
<name sortKey="Rose, Faith J" sort="Rose, Faith J" uniqKey="Rose F" first="Faith J" last="Rose">Faith J. Rose</name>
<name sortKey="Thomson, Robin J" sort="Thomson, Robin J" uniqKey="Thomson R" first="Robin J" last="Thomson">Robin J. Thomson</name>
<name sortKey="Von Itzstein, Mark" sort="Von Itzstein, Mark" uniqKey="Von Itzstein M" first="Mark" last="Von Itzstein">Mark Von Itzstein</name>
</country>
<country name="France"><noRegion><name sortKey="Rameix Welti, Marie Anne" sort="Rameix Welti, Marie Anne" uniqKey="Rameix Welti M" first="Marie-Anne" last="Rameix-Welti">Marie-Anne Rameix-Welti</name>
</noRegion>
<name sortKey="Naffakh, Nadia" sort="Naffakh, Nadia" uniqKey="Naffakh N" first="Nadia" last="Naffakh">Nadia Naffakh</name>
<name sortKey="Van Der Werf, Sylvie" sort="Van Der Werf, Sylvie" uniqKey="Van Der Werf S" first="Sylvie" last="Van Der Werf">Sylvie Van Der Werf</name>
</country>
<country name="Royaume-Uni"><noRegion><name sortKey="Kerry, Philip S" sort="Kerry, Philip S" uniqKey="Kerry P" first="Philip S" last="Kerry">Philip S. Kerry</name>
</noRegion>
<name sortKey="Russell, Rupert J M" sort="Russell, Rupert J M" uniqKey="Russell R" first="Rupert J M" last="Russell">Rupert J M. Russell</name>
</country>
</tree>
</affiliations>
</record>

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Novel sialic acid derivatives lock open the 150-loop of an influenza A virus group-1 sialidase.

Novel sialic acid derivatives lock open the 150-loop of an influenza A virus group-1 sialidase.

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