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A novel peptide with potent and broad-spectrum antiviral activities against multiple respiratory viruses

Identifieur interne : 000742 ( Pmc/Checkpoint ); précédent : 000741; suivant : 000743

A novel peptide with potent and broad-spectrum antiviral activities against multiple respiratory viruses

Auteurs : Hanjun Zhao [République populaire de Chine] ; Jie Zhou [République populaire de Chine] ; Ke Zhang [République populaire de Chine] ; Hin Chu [République populaire de Chine] ; Dabin Liu [République populaire de Chine] ; Vincent Kwok-Man Poon [République populaire de Chine] ; Chris Chung-Sing Chan [République populaire de Chine] ; Ho-Chuen Leung [République populaire de Chine] ; Ng Fai [République populaire de Chine] ; Yong-Ping Lin [République populaire de Chine] ; Anna Jin-Xia Zhang [République populaire de Chine] ; Dong-Yan Jin [République populaire de Chine] ; Kwok-Yung Yuen [République populaire de Chine] ; Bo-Jian Zheng [République populaire de Chine]

Source :

RBID : PMC:4766503

Abstract

A safe, potent and broad-spectrum antiviral is urgently needed to combat emerging respiratory viruses. In light of the broad antiviral activity of β-defensins, we tested the antiviral activity of 11 peptides derived from mouse β-defensin-4 and found that a short peptide, P9, exhibited potent and broad-spectrum antiviral effects against multiple respiratory viruses in vitro and in vivo, including influenza A virus H1N1, H3N2, H5N1, H7N7, H7N9, SARS-CoV and MERS-CoV. The antiviral activity of P9 was attributed to its high-affinity binding to viral glycoproteins, as well as the abundance of basic amino acids in its composition. After binding viral particles through viral surface glycoproteins, P9 entered into cells together with the viruses via endocytosis and prevented endosomal acidification, which blocked membrane fusion and subsequent viral RNA release. This study has paved the avenue for developing new prophylactic and therapeutic agents with broad-spectrum antiviral activities.

Electronic supplementary material

The online version of this article (doi:10.1038/srep22008) contains supplementary material, which is available to authorized users.


Url:
DOI: 10.1038/srep22008
PubMed: 26911565
PubMed Central: 4766503


Affiliations:


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PMC:4766503

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<p>A safe, potent and broad-spectrum antiviral is urgently needed to combat emerging respiratory viruses. In light of the broad antiviral activity of β-defensins, we tested the antiviral activity of 11 peptides derived from mouse β-defensin-4 and found that a short peptide, P9, exhibited potent and broad-spectrum antiviral effects against multiple respiratory viruses
<italic>in vitro</italic>
and
<italic>in vivo</italic>
, including influenza A virus H1N1, H3N2, H5N1, H7N7, H7N9, SARS-CoV and MERS-CoV. The antiviral activity of P9 was attributed to its high-affinity binding to viral glycoproteins, as well as the abundance of basic amino acids in its composition. After binding viral particles through viral surface glycoproteins, P9 entered into cells together with the viruses via endocytosis and prevented endosomal acidification, which blocked membrane fusion and subsequent viral RNA release. This study has paved the avenue for developing new prophylactic and therapeutic agents with broad-spectrum antiviral activities.</p>
<sec>
<title>Electronic supplementary material</title>
<p>The online version of this article (doi:10.1038/srep22008) contains supplementary material, which is available to authorized users.</p>
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<journal-id journal-id-type="iso-abbrev">Sci Rep</journal-id>
<journal-title-group>
<journal-title>Scientific Reports</journal-title>
</journal-title-group>
<issn pub-type="epub">2045-2322</issn>
<publisher>
<publisher-name>Nature Publishing Group UK</publisher-name>
<publisher-loc>London</publisher-loc>
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<article-id pub-id-type="pmc">4766503</article-id>
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<article-id pub-id-type="doi">10.1038/srep22008</article-id>
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<subject>Article</subject>
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<title-group>
<article-title>A novel peptide with potent and broad-spectrum antiviral activities against multiple respiratory viruses</article-title>
</title-group>
<contrib-group>
<contrib contrib-type="author">
<name>
<surname>Zhao</surname>
<given-names>Hanjun</given-names>
</name>
<xref ref-type="aff" rid="Aff1">1</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Zhou</surname>
<given-names>Jie</given-names>
</name>
<xref ref-type="aff" rid="Aff1">1</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Zhang</surname>
<given-names>Ke</given-names>
</name>
<xref ref-type="aff" rid="Aff1">1</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Chu</surname>
<given-names>Hin</given-names>
</name>
<xref ref-type="aff" rid="Aff1">1</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Liu</surname>
<given-names>Dabin</given-names>
</name>
<xref ref-type="aff" rid="Aff1">1</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Poon</surname>
<given-names>Vincent Kwok-Man</given-names>
</name>
<xref ref-type="aff" rid="Aff1">1</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Chan</surname>
<given-names>Chris Chung-Sing</given-names>
</name>
<xref ref-type="aff" rid="Aff1">1</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Leung</surname>
<given-names>Ho-Chuen</given-names>
</name>
<xref ref-type="aff" rid="Aff1">1</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Fai</surname>
<given-names>Ng</given-names>
</name>
<xref ref-type="aff" rid="Aff1">1</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Lin</surname>
<given-names>Yong-Ping</given-names>
</name>
<xref ref-type="aff" rid="Aff1">1</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Zhang</surname>
<given-names>Anna Jin-Xia</given-names>
</name>
<xref ref-type="aff" rid="Aff1">1</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Jin</surname>
<given-names>Dong-Yan</given-names>
</name>
<xref ref-type="aff" rid="Aff2">2</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Yuen</surname>
<given-names>Kwok-Yung</given-names>
</name>
<xref ref-type="aff" rid="Aff1">1</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Zheng</surname>
<given-names>Bo-Jian</given-names>
</name>
<address>
<email>bzheng@hkucc.hku.hk</email>
</address>
<xref ref-type="aff" rid="Aff1">1</xref>
</contrib>
<aff id="Aff1">
<label>1</label>
<institution-wrap>
<institution-id institution-id-type="GRID">grid.194645.b</institution-id>
<institution-id institution-id-type="ISNI">0000000121742757</institution-id>
<institution>Department of Microbiology,</institution>
<institution>The University of Hong Kong,</institution>
</institution-wrap>
Hong Kong, China</aff>
<aff id="Aff2">
<label>2</label>
<institution-wrap>
<institution-id institution-id-type="GRID">grid.194645.b</institution-id>
<institution-id institution-id-type="ISNI">0000000121742757</institution-id>
<institution>School of Biomedical Sciences, The University of Hong Kong,</institution>
</institution-wrap>
Hong Kong, China</aff>
</contrib-group>
<pub-date pub-type="epub">
<day>25</day>
<month>2</month>
<year>2016</year>
</pub-date>
<pub-date pub-type="pmc-release">
<day>25</day>
<month>2</month>
<year>2016</year>
</pub-date>
<pub-date pub-type="collection">
<year>2016</year>
</pub-date>
<volume>6</volume>
<elocation-id>22008</elocation-id>
<history>
<date date-type="received">
<day>4</day>
<month>11</month>
<year>2015</year>
</date>
<date date-type="accepted">
<day>3</day>
<month>2</month>
<year>2016</year>
</date>
</history>
<permissions>
<copyright-statement>© The Author(s) 2016</copyright-statement>
<license license-type="OpenAccess">
<license-p>This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit
<ext-link ext-link-type="uri" xlink:href="http://creativecommons.org/licenses/by/4.0/">http://creativecommons.org/licenses/by/4.0/</ext-link>
</license-p>
</license>
</permissions>
<abstract id="Abs1">
<p>A safe, potent and broad-spectrum antiviral is urgently needed to combat emerging respiratory viruses. In light of the broad antiviral activity of β-defensins, we tested the antiviral activity of 11 peptides derived from mouse β-defensin-4 and found that a short peptide, P9, exhibited potent and broad-spectrum antiviral effects against multiple respiratory viruses
<italic>in vitro</italic>
and
<italic>in vivo</italic>
, including influenza A virus H1N1, H3N2, H5N1, H7N7, H7N9, SARS-CoV and MERS-CoV. The antiviral activity of P9 was attributed to its high-affinity binding to viral glycoproteins, as well as the abundance of basic amino acids in its composition. After binding viral particles through viral surface glycoproteins, P9 entered into cells together with the viruses via endocytosis and prevented endosomal acidification, which blocked membrane fusion and subsequent viral RNA release. This study has paved the avenue for developing new prophylactic and therapeutic agents with broad-spectrum antiviral activities.</p>
<sec>
<title>Electronic supplementary material</title>
<p>The online version of this article (doi:10.1038/srep22008) contains supplementary material, which is available to authorized users.</p>
</sec>
</abstract>
<kwd-group kwd-group-type="npg-subject">
<title>Subject terms</title>
<kwd>Drug discovery</kwd>
<kwd>Antiviral agents</kwd>
</kwd-group>
<custom-meta-group>
<custom-meta>
<meta-name>issue-copyright-statement</meta-name>
<meta-value>© The Author(s) 2016</meta-value>
</custom-meta>
</custom-meta-group>
</article-meta>
</front>
</pmc>
<affiliations>
<list>
<country>
<li>République populaire de Chine</li>
</country>
</list>
<tree>
<country name="République populaire de Chine">
<noRegion>
<name sortKey="Zhao, Hanjun" sort="Zhao, Hanjun" uniqKey="Zhao H" first="Hanjun" last="Zhao">Hanjun Zhao</name>
</noRegion>
<name sortKey="Chan, Chris Chung Sing" sort="Chan, Chris Chung Sing" uniqKey="Chan C" first="Chris Chung-Sing" last="Chan">Chris Chung-Sing Chan</name>
<name sortKey="Chu, Hin" sort="Chu, Hin" uniqKey="Chu H" first="Hin" last="Chu">Hin Chu</name>
<name sortKey="Fai, Ng" sort="Fai, Ng" uniqKey="Fai N" first="Ng" last="Fai">Ng Fai</name>
<name sortKey="Jin, Dong Yan" sort="Jin, Dong Yan" uniqKey="Jin D" first="Dong-Yan" last="Jin">Dong-Yan Jin</name>
<name sortKey="Leung, Ho Chuen" sort="Leung, Ho Chuen" uniqKey="Leung H" first="Ho-Chuen" last="Leung">Ho-Chuen Leung</name>
<name sortKey="Lin, Yong Ping" sort="Lin, Yong Ping" uniqKey="Lin Y" first="Yong-Ping" last="Lin">Yong-Ping Lin</name>
<name sortKey="Liu, Dabin" sort="Liu, Dabin" uniqKey="Liu D" first="Dabin" last="Liu">Dabin Liu</name>
<name sortKey="Poon, Vincent Kwok Man" sort="Poon, Vincent Kwok Man" uniqKey="Poon V" first="Vincent Kwok-Man" last="Poon">Vincent Kwok-Man Poon</name>
<name sortKey="Yuen, Kwok Yung" sort="Yuen, Kwok Yung" uniqKey="Yuen K" first="Kwok-Yung" last="Yuen">Kwok-Yung Yuen</name>
<name sortKey="Zhang, Anna Jin Xia" sort="Zhang, Anna Jin Xia" uniqKey="Zhang A" first="Anna Jin-Xia" last="Zhang">Anna Jin-Xia Zhang</name>
<name sortKey="Zhang, Ke" sort="Zhang, Ke" uniqKey="Zhang K" first="Ke" last="Zhang">Ke Zhang</name>
<name sortKey="Zheng, Bo Jian" sort="Zheng, Bo Jian" uniqKey="Zheng B" first="Bo-Jian" last="Zheng">Bo-Jian Zheng</name>
<name sortKey="Zhou, Jie" sort="Zhou, Jie" uniqKey="Zhou J" first="Jie" last="Zhou">Jie Zhou</name>
</country>
</tree>
</affiliations>
</record>

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