Porcine epidemic diarrhea virus papain-like protease 2 can be noncompetitively inhibited by 6-thioguanine
Identifieur interne : 000499 ( Pmc/Checkpoint ); précédent : 000498; suivant : 000500Porcine epidemic diarrhea virus papain-like protease 2 can be noncompetitively inhibited by 6-thioguanine
Auteurs : Hsu-Feng Chu [Taïwan] ; Chiao-Che Chen [Taïwan] ; David C. Moses [Taïwan] ; Yau-Hung Chen [Taïwan] ; Chao-Hsiung Lin [Taïwan] ; Ying-Chieh Tsai [Taïwan] ; Chi-Yuan Chou [Taïwan]Source :
- Antiviral Research [ 0166-3542 ] ; 2018.
Abstract
Porcine epidemic diarrhea virus (PEDV) is a coronavirus (CoV) discovered in the 1970s that infects the intestinal tract of pigs, resulting in diarrhea and vomiting. It can cause extreme dehydration and death in neonatal piglets. In Asia, modified live attenuated vaccines have been used to control PEDV infection in recent years. However, a new strain of PEDV that belongs to genogroup 2a appeared in the USA in 2013 and then quickly spread to Canada and Mexico as well as Asian and European countries. Due to the less effective protective immunity provided by the vaccines against this new strain, it has caused considerable agricultural and economic loss worldwide. The emergence of this new strain increases the importance of understanding PEDV as well as strategies for inhibiting it. Coronaviral proteases, including main proteases and papain-like proteases, are ideal antiviral targets because of their essential roles in viral maturation. Here we provide a first description of the expression, purification and structural characteristics of recombinant PEDV papain-like protease 2, moreover present our finding that 6-thioguanine, a chemotherapeutic drug, in contrast to its competitive inhibition on SARS- and MERS-CoV papain-like proteases, is a noncompetitive inhibitor of PEDV papain-like protease 2.
Url:
DOI: 10.1016/j.antiviral.2018.08.011
PubMed: 30138642
PubMed Central: 7113753
Affiliations:
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type="doi">10.1016/j.antiviral.2018.08.011</idno><date when="2018">2018</date><idno type="wicri:Area/Pmc/Corpus">000A68</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Corpus" wicri:corpus="PMC">000A68</idno><idno type="wicri:Area/Pmc/Curation">000A68</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Curation">000A68</idno><idno type="wicri:Area/Pmc/Checkpoint">000499</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Checkpoint">000499</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">Porcine epidemic diarrhea virus papain-like protease 2 can be noncompetitively inhibited by 6-thioguanine</title><author><name sortKey="Chu, Hsu Feng" sort="Chu, Hsu Feng" uniqKey="Chu H" first="Hsu-Feng" last="Chu">Hsu-Feng Chu</name><affiliation wicri:level="1"><nlm:aff id="aff1">Biomedical Industry Ph.D. Program, National Yang-Ming University, Taipei 112, Taiwan</nlm:aff><country xml:lang="fr">Taïwan</country><wicri:regionArea>Biomedical Industry Ph.D. Program, National Yang-Ming University, Taipei 112</wicri:regionArea><wicri:noRegion>Taipei 112</wicri:noRegion></affiliation><affiliation wicri:level="1"><nlm:aff id="aff2">Department of Life Sciences and Institute of Genome Sciences, National Yang-Ming University, Taipei 112, Taiwan</nlm:aff><country xml:lang="fr">Taïwan</country><wicri:regionArea>Department of Life Sciences and Institute of Genome Sciences, National Yang-Ming University, Taipei 112</wicri:regionArea><wicri:noRegion>Taipei 112</wicri:noRegion></affiliation></author><author><name sortKey="Chen, Chiao Che" sort="Chen, Chiao Che" uniqKey="Chen C" first="Chiao-Che" last="Chen">Chiao-Che Chen</name><affiliation wicri:level="1"><nlm:aff id="aff2">Department of Life Sciences and Institute of Genome Sciences, National Yang-Ming University, Taipei 112, Taiwan</nlm:aff><country xml:lang="fr">Taïwan</country><wicri:regionArea>Department of Life Sciences and Institute of Genome Sciences, National Yang-Ming University, Taipei 112</wicri:regionArea><wicri:noRegion>Taipei 112</wicri:noRegion></affiliation></author><author><name sortKey="Moses, David C" sort="Moses, David C" uniqKey="Moses D" first="David C." last="Moses">David C. Moses</name><affiliation wicri:level="1"><nlm:aff id="aff3">Department of Chemistry, Tamkang University, Tamsui 251, Taiwan</nlm:aff><country xml:lang="fr">Taïwan</country><wicri:regionArea>Department of Chemistry, Tamkang University, Tamsui 251</wicri:regionArea><wicri:noRegion>Tamsui 251</wicri:noRegion></affiliation></author><author><name sortKey="Chen, Yau Hung" sort="Chen, Yau Hung" uniqKey="Chen Y" first="Yau-Hung" last="Chen">Yau-Hung Chen</name><affiliation wicri:level="1"><nlm:aff id="aff3">Department of Chemistry, Tamkang University, Tamsui 251, Taiwan</nlm:aff><country xml:lang="fr">Taïwan</country><wicri:regionArea>Department of Chemistry, Tamkang University, Tamsui 251</wicri:regionArea><wicri:noRegion>Tamsui 251</wicri:noRegion></affiliation></author><author><name sortKey="Lin, Chao Hsiung" sort="Lin, Chao Hsiung" uniqKey="Lin C" first="Chao-Hsiung" last="Lin">Chao-Hsiung Lin</name><affiliation wicri:level="1"><nlm:aff id="aff2">Department of Life Sciences and Institute of Genome Sciences, National Yang-Ming University, Taipei 112, Taiwan</nlm:aff><country xml:lang="fr">Taïwan</country><wicri:regionArea>Department of Life Sciences and Institute of Genome Sciences, National Yang-Ming University, Taipei 112</wicri:regionArea><wicri:noRegion>Taipei 112</wicri:noRegion></affiliation></author><author><name sortKey="Tsai, Ying Chieh" sort="Tsai, Ying Chieh" uniqKey="Tsai Y" first="Ying-Chieh" last="Tsai">Ying-Chieh Tsai</name><affiliation wicri:level="1"><nlm:aff id="aff4">Institute of Biochemistry and Molecular Biology, National Yang-Ming University, Taipei 112, Taiwan</nlm:aff><country xml:lang="fr">Taïwan</country><wicri:regionArea>Institute of Biochemistry and Molecular Biology, National Yang-Ming University, Taipei 112</wicri:regionArea><wicri:noRegion>Taipei 112</wicri:noRegion></affiliation><affiliation wicri:level="1"><nlm:aff id="aff5">Probiotic Research Center, National Yang-Ming University, Taipei 112, Taiwan</nlm:aff><country xml:lang="fr">Taïwan</country><wicri:regionArea>Probiotic Research Center, National Yang-Ming University, Taipei 112</wicri:regionArea><wicri:noRegion>Taipei 112</wicri:noRegion></affiliation></author><author><name sortKey="Chou, Chi Yuan" sort="Chou, Chi Yuan" uniqKey="Chou C" first="Chi-Yuan" last="Chou">Chi-Yuan Chou</name><affiliation wicri:level="1"><nlm:aff id="aff2">Department of Life Sciences and Institute of Genome Sciences, National Yang-Ming University, Taipei 112, Taiwan</nlm:aff><country xml:lang="fr">Taïwan</country><wicri:regionArea>Department of Life Sciences and Institute of Genome Sciences, National Yang-Ming University, Taipei 112</wicri:regionArea><wicri:noRegion>Taipei 112</wicri:noRegion></affiliation></author></analytic><series><title level="j">Antiviral Research</title><idno type="ISSN">0166-3542</idno><idno type="eISSN">1872-9096</idno><imprint><date when="2018">2018</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><p>Porcine epidemic diarrhea virus (PEDV) is a coronavirus (CoV) discovered in the 1970s that infects the intestinal tract of pigs, resulting in diarrhea and vomiting. It can cause extreme dehydration and death in neonatal piglets. In Asia, modified live attenuated vaccines have been used to control PEDV infection in recent years. However, a new strain of PEDV that belongs to genogroup 2a appeared in the USA in 2013 and then quickly spread to Canada and Mexico as well as Asian and European countries. Due to the less effective protective immunity provided by the vaccines against this new strain, it has caused considerable agricultural and economic loss worldwide. The emergence of this new strain increases the importance of understanding PEDV as well as strategies for inhibiting it. Coronaviral proteases, including main proteases and papain-like proteases, are ideal antiviral targets because of their essential roles in viral maturation. Here we provide a first description of the expression, purification and structural characteristics of recombinant PEDV papain-like protease 2, moreover present our finding that 6-thioguanine, a chemotherapeutic drug, in contrast to its competitive inhibition on SARS- and MERS-CoV papain-like proteases, is a noncompetitive inhibitor of PEDV papain-like protease 2.</p></div></front><back><div1 type="bibliography"><listBibl><biblStruct><analytic><author><name sortKey="Anand, K" uniqKey="Anand K">K. Anand</name></author><author><name sortKey="Ziebuhr, J" uniqKey="Ziebuhr J">J. Ziebuhr</name></author><author><name sortKey="Wadhwani, P" uniqKey="Wadhwani P">P. Wadhwani</name></author><author><name sortKey="Mesters, J R" uniqKey="Mesters J">J.R. Mesters</name></author><author><name sortKey="Hilgenfeld, R" uniqKey="Hilgenfeld R">R. Hilgenfeld</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Arnold, K" uniqKey="Arnold K">K. 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<front><journal-meta><journal-id journal-id-type="nlm-ta">Antiviral Res</journal-id><journal-id journal-id-type="iso-abbrev">Antiviral Res</journal-id><journal-title-group><journal-title>Antiviral Research</journal-title></journal-title-group><issn pub-type="ppub">0166-3542</issn><issn pub-type="epub">1872-9096</issn><publisher><publisher-name>Elsevier B.V.</publisher-name></publisher></journal-meta><article-meta><article-id pub-id-type="pmid">30138642</article-id><article-id pub-id-type="pmc">7113753</article-id><article-id pub-id-type="publisher-id">S0166-3542(18)30218-3</article-id><article-id pub-id-type="doi">10.1016/j.antiviral.2018.08.011</article-id><article-categories><subj-group subj-group-type="heading"><subject>Article</subject></subj-group></article-categories><title-group><article-title>Porcine epidemic diarrhea virus papain-like protease 2 can be noncompetitively inhibited by 6-thioguanine</article-title></title-group><contrib-group><contrib contrib-type="author" id="au1"><name><surname>Chu</surname><given-names>Hsu-Feng</given-names></name><xref rid="aff1" ref-type="aff">a</xref><xref rid="aff2" ref-type="aff">b</xref></contrib><contrib contrib-type="author" id="au2"><name><surname>Chen</surname><given-names>Chiao-Che</given-names></name><xref rid="aff2" ref-type="aff">b</xref></contrib><contrib contrib-type="author" id="au3"><name><surname>Moses</surname><given-names>David C.</given-names></name><xref rid="aff3" ref-type="aff">c</xref></contrib><contrib contrib-type="author" id="au4"><name><surname>Chen</surname><given-names>Yau-Hung</given-names></name><xref rid="aff3" ref-type="aff">c</xref></contrib><contrib contrib-type="author" id="au5"><name><surname>Lin</surname><given-names>Chao-Hsiung</given-names></name><xref rid="aff2" ref-type="aff">b</xref></contrib><contrib contrib-type="author" id="au6"><name><surname>Tsai</surname><given-names>Ying-Chieh</given-names></name><xref rid="aff4" ref-type="aff">d</xref><xref rid="aff5" ref-type="aff">e</xref></contrib><contrib contrib-type="author" id="au7"><name><surname>Chou</surname><given-names>Chi-Yuan</given-names></name><email>cychou@ym.edu.tw</email><xref rid="aff2" ref-type="aff">b</xref><xref rid="cor1" ref-type="corresp">∗</xref></contrib></contrib-group><aff id="aff1"><label>a</label>Biomedical Industry Ph.D. Program, National Yang-Ming University, Taipei 112, Taiwan</aff><aff id="aff2"><label>b</label>Department of Life Sciences and Institute of Genome Sciences, National Yang-Ming University, Taipei 112, Taiwan</aff><aff id="aff3"><label>c</label>Department of Chemistry, Tamkang University, Tamsui 251, Taiwan</aff><aff id="aff4"><label>d</label>Institute of Biochemistry and Molecular Biology, National Yang-Ming University, Taipei 112, Taiwan</aff><aff id="aff5"><label>e</label>Probiotic Research Center, National Yang-Ming University, Taipei 112, Taiwan</aff><author-notes><corresp id="cor1"><label>∗</label>Corresponding author. 155 Li-Nong St., Sec. 2, Taipei 112, Taiwan. <email>cychou@ym.edu.tw</email></corresp></author-notes><pub-date pub-type="pmc-release"><day>20</day><month>8</month><year>2018</year></pub-date><pmc-comment> PMC Release delay is 0 months and 0 days and was based on .</pmc-comment>
<pub-date pub-type="ppub"><month>10</month><year>2018</year></pub-date><pub-date pub-type="epub"><day>20</day><month>8</month><year>2018</year></pub-date><volume>158</volume><fpage>199</fpage><lpage>205</lpage><history><date date-type="received"><day>18</day><month>4</month><year>2018</year></date><date date-type="rev-recd"><day>9</day><month>7</month><year>2018</year></date><date date-type="accepted"><day>17</day><month>8</month><year>2018</year></date></history><permissions><copyright-statement>© 2018 Elsevier B.V. All rights reserved.</copyright-statement><copyright-year>2018</copyright-year><copyright-holder>Elsevier B.V.</copyright-holder><license><license-p>Since January 2020 Elsevier has created a COVID-19 resource centre with free information in English and Mandarin on the novel coronavirus COVID-19. The COVID-19 resource centre is hosted on Elsevier Connect, the company's public news and information website. Elsevier hereby grants permission to make all its COVID-19-related research that is available on the COVID-19 resource centre - including this research content - immediately available in PubMed Central and other publicly funded repositories, such as the WHO COVID database with rights for unrestricted research re-use and analyses in any form or by any means with acknowledgement of the original source. These permissions are granted for free by Elsevier for as long as the COVID-19 resource centre remains active.</license-p></license></permissions><abstract id="abs0010"><p>Porcine epidemic diarrhea virus (PEDV) is a coronavirus (CoV) discovered in the 1970s that infects the intestinal tract of pigs, resulting in diarrhea and vomiting. It can cause extreme dehydration and death in neonatal piglets. In Asia, modified live attenuated vaccines have been used to control PEDV infection in recent years. However, a new strain of PEDV that belongs to genogroup 2a appeared in the USA in 2013 and then quickly spread to Canada and Mexico as well as Asian and European countries. Due to the less effective protective immunity provided by the vaccines against this new strain, it has caused considerable agricultural and economic loss worldwide. The emergence of this new strain increases the importance of understanding PEDV as well as strategies for inhibiting it. Coronaviral proteases, including main proteases and papain-like proteases, are ideal antiviral targets because of their essential roles in viral maturation. Here we provide a first description of the expression, purification and structural characteristics of recombinant PEDV papain-like protease 2, moreover present our finding that 6-thioguanine, a chemotherapeutic drug, in contrast to its competitive inhibition on SARS- and MERS-CoV papain-like proteases, is a noncompetitive inhibitor of PEDV papain-like protease 2.</p></abstract><abstract abstract-type="author-highlights" id="abs0015"><title>Highlights</title><p><list list-type="simple" id="ulist0010"><list-item id="u0010"><label>•</label><p id="p0010">PEDV PL2<sup>pro</sup> exhibits much higher DUB activity than that of other PL<sup>pro</sup>s in spite of their structural similarities.</p></list-item><list-item id="u0015"><label>•</label><p id="p0015">In contrast to its competitive inhibition on SARS- and MERS-CoV PL<sup>pro</sup>s, 6-thioguanine inhibits PEDV PL2<sup>pro</sup> allosterically.</p></list-item><list-item id="u0020"><label>•</label><p id="p0020">Putative 6-thioguanine binding site is proposed to render the blocking loop less flexible and therefore disfavor catalysis.</p></list-item><list-item id="u0025"><label>•</label><p id="p0025">6-thioguanine can be a lead compound for anti-coronaviral drug development.</p></list-item></list></p></abstract><kwd-group id="kwrds0010"><title>Keywords</title><kwd>PEDV</kwd><kwd>Papain-like protease</kwd><kwd>6-Thioguanine</kwd><kwd>Noncompetitive inhibition</kwd><kwd>Alpha coronavirus</kwd></kwd-group><kwd-group id="kwrds0015"><title>Abbreviations</title><kwd>AUC, The abbreviations used are analytical ultracentrifugation</kwd><kwd>CoV, coronavirus</kwd><kwd>DUB, deubiquitinating</kwd><kwd>MERS, Middle East respiratory syndrome</kwd><kwd>βME, β-mercaptoethanol</kwd><kwd>6MP, 6-mercaptopurine</kwd><kwd>nsp, non-structural protein</kwd><kwd>PL<sup>pro</sup>, papain-like protease</kwd><kwd>PL1<sup>pro</sup>, papain-like protease 1</kwd><kwd>PL2<sup>pro</sup>, papain-like protease 2</kwd><kwd>PEDV, porcine epidemic diarrhea virus</kwd><kwd>6TG, 6-thioguanine</kwd><kwd>SARS, severe acute respiratory syndrome</kwd><kwd>SV, sedimentation velocity</kwd><kwd>Ubl, ubiquitin-like</kwd><kwd>Ub-AFC, ubiquitin-7-amino-4-trifluoro-methyl-coumarin</kwd><kwd>USP, ubiquitin-specific protease</kwd></kwd-group></article-meta></front></pmc><affiliations><list><country><li>Taïwan</li></country></list><tree><country name="Taïwan"><noRegion><name sortKey="Chu, Hsu Feng" sort="Chu, Hsu Feng" uniqKey="Chu H" first="Hsu-Feng" last="Chu">Hsu-Feng Chu</name></noRegion><name sortKey="Chen, Chiao Che" sort="Chen, Chiao Che" uniqKey="Chen C" first="Chiao-Che" last="Chen">Chiao-Che Chen</name><name sortKey="Chen, Yau Hung" sort="Chen, Yau Hung" uniqKey="Chen Y" first="Yau-Hung" last="Chen">Yau-Hung Chen</name><name sortKey="Chou, Chi Yuan" sort="Chou, Chi Yuan" uniqKey="Chou C" first="Chi-Yuan" last="Chou">Chi-Yuan Chou</name><name sortKey="Chu, Hsu Feng" sort="Chu, Hsu Feng" uniqKey="Chu H" first="Hsu-Feng" last="Chu">Hsu-Feng Chu</name><name sortKey="Lin, Chao Hsiung" sort="Lin, Chao Hsiung" uniqKey="Lin C" first="Chao-Hsiung" last="Lin">Chao-Hsiung Lin</name><name sortKey="Moses, David C" sort="Moses, David C" uniqKey="Moses D" first="David C." last="Moses">David C. Moses</name><name sortKey="Tsai, Ying Chieh" sort="Tsai, Ying Chieh" uniqKey="Tsai Y" first="Ying-Chieh" last="Tsai">Ying-Chieh Tsai</name><name sortKey="Tsai, Ying Chieh" sort="Tsai, Ying Chieh" uniqKey="Tsai Y" first="Ying-Chieh" last="Tsai">Ying-Chieh Tsai</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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