Thiopurine analogs and mycophenolic acid synergistically inhibit the papain-like protease of Middle East respiratory syndrome coronavirus
Identifieur interne : 000A59 ( Pmc/Curation ); précédent : 000A58; suivant : 000A60Thiopurine analogs and mycophenolic acid synergistically inhibit the papain-like protease of Middle East respiratory syndrome coronavirus
Auteurs : Kai-Wen Cheng [Taïwan] ; Shu-Chun Cheng [Taïwan] ; Wei-Yi Chen [Taïwan] ; Min-Han Lin [Taïwan] ; Shang-Ju Chuang [Taïwan] ; I-Hsin Cheng [Taïwan] ; Chiao-Yin Sun [Taïwan] ; Chi-Yuan Chou [Taïwan]Source :
- Antiviral Research [ 0166-3542 ] ; 2014.
Abstract
6-Mercaptopurine and 6-thioguanine are competitive inhibitors of SARS-CoV and MERS-CoV papain-like proteases. Mycophenolic acid can noncompetitively inhibit papain-like protease of MERS-CoV, while cannot inhibit that of SARS-CoV. 6-Mercaptopurine/6-thioguanine and mycophenolic acid synergistically inhibit MERS-CoV papain-like protease. The three drugs with inhibitory effect for MERS-CoV papain-like protease can be used as lead compounds for drug development.
Url:
DOI: 10.1016/j.antiviral.2014.12.011
PubMed: 25542975
PubMed Central: 7113672
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<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">Thiopurine analogs and mycophenolic acid synergistically inhibit the papain-like protease of Middle East respiratory syndrome coronavirus</title><author><name sortKey="Cheng, Kai Wen" sort="Cheng, Kai Wen" uniqKey="Cheng K" first="Kai-Wen" last="Cheng">Kai-Wen Cheng</name><affiliation wicri:level="1"><nlm:aff id="af005">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></affiliation></author><author><name sortKey="Cheng, Shu Chun" sort="Cheng, Shu Chun" uniqKey="Cheng S" first="Shu-Chun" last="Cheng">Shu-Chun Cheng</name><affiliation wicri:level="1"><nlm:aff id="af010">Department of Nephrology, Chang-Gung Memorial Hospital, Keelung 204, Taiwan</nlm:aff><country xml:lang="fr">Taïwan</country><wicri:regionArea>Department of Nephrology, Chang-Gung Memorial Hospital, Keelung 204</wicri:regionArea></affiliation></author><author><name sortKey="Chen, Wei Yi" sort="Chen, Wei Yi" uniqKey="Chen W" first="Wei-Yi" last="Chen">Wei-Yi Chen</name><affiliation wicri:level="1"><nlm:aff id="af015">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></affiliation></author><author><name sortKey="Lin, Min Han" sort="Lin, Min Han" uniqKey="Lin M" first="Min-Han" last="Lin">Min-Han Lin</name><affiliation wicri:level="1"><nlm:aff id="af005">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></affiliation></author><author><name sortKey="Chuang, Shang Ju" sort="Chuang, Shang Ju" uniqKey="Chuang S" first="Shang-Ju" last="Chuang">Shang-Ju Chuang</name><affiliation wicri:level="1"><nlm:aff id="af005">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></affiliation></author><author><name sortKey="Cheng, I Hsin" sort="Cheng, I Hsin" uniqKey="Cheng I" first="I-Hsin" last="Cheng">I-Hsin Cheng</name><affiliation wicri:level="1"><nlm:aff id="af015">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></affiliation></author><author><name sortKey="Sun, Chiao Yin" sort="Sun, Chiao Yin" uniqKey="Sun C" first="Chiao-Yin" last="Sun">Chiao-Yin Sun</name><affiliation wicri:level="1"><nlm:aff id="af010">Department of Nephrology, Chang-Gung Memorial Hospital, Keelung 204, Taiwan</nlm:aff><country xml:lang="fr">Taïwan</country><wicri:regionArea>Department of Nephrology, Chang-Gung Memorial Hospital, Keelung 204</wicri:regionArea></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="af005">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></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PMC</idno><idno type="pmid">25542975</idno><idno type="pmc">7113672</idno><idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7113672</idno><idno type="RBID">PMC:7113672</idno><idno type="doi">10.1016/j.antiviral.2014.12.011</idno><date when="2014">2014</date><idno type="wicri:Area/Pmc/Corpus">000A59</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Corpus" wicri:corpus="PMC">000A59</idno><idno type="wicri:Area/Pmc/Curation">000A59</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Curation">000A59</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">Thiopurine analogs and mycophenolic acid synergistically inhibit the papain-like protease of Middle East respiratory syndrome coronavirus</title><author><name sortKey="Cheng, Kai Wen" sort="Cheng, Kai Wen" uniqKey="Cheng K" first="Kai-Wen" last="Cheng">Kai-Wen Cheng</name><affiliation wicri:level="1"><nlm:aff id="af005">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></affiliation></author><author><name sortKey="Cheng, Shu Chun" sort="Cheng, Shu Chun" uniqKey="Cheng S" first="Shu-Chun" last="Cheng">Shu-Chun Cheng</name><affiliation wicri:level="1"><nlm:aff id="af010">Department of Nephrology, Chang-Gung Memorial Hospital, Keelung 204, Taiwan</nlm:aff><country xml:lang="fr">Taïwan</country><wicri:regionArea>Department of Nephrology, Chang-Gung Memorial Hospital, Keelung 204</wicri:regionArea></affiliation></author><author><name sortKey="Chen, Wei Yi" sort="Chen, Wei Yi" uniqKey="Chen W" first="Wei-Yi" last="Chen">Wei-Yi Chen</name><affiliation wicri:level="1"><nlm:aff id="af015">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></affiliation></author><author><name sortKey="Lin, Min Han" sort="Lin, Min Han" uniqKey="Lin M" first="Min-Han" last="Lin">Min-Han Lin</name><affiliation wicri:level="1"><nlm:aff id="af005">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></affiliation></author><author><name sortKey="Chuang, Shang Ju" sort="Chuang, Shang Ju" uniqKey="Chuang S" first="Shang-Ju" last="Chuang">Shang-Ju Chuang</name><affiliation wicri:level="1"><nlm:aff id="af005">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></affiliation></author><author><name sortKey="Cheng, I Hsin" sort="Cheng, I Hsin" uniqKey="Cheng I" first="I-Hsin" last="Cheng">I-Hsin Cheng</name><affiliation wicri:level="1"><nlm:aff id="af015">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></affiliation></author><author><name sortKey="Sun, Chiao Yin" sort="Sun, Chiao Yin" uniqKey="Sun C" first="Chiao-Yin" last="Sun">Chiao-Yin Sun</name><affiliation wicri:level="1"><nlm:aff id="af010">Department of Nephrology, Chang-Gung Memorial Hospital, Keelung 204, Taiwan</nlm:aff><country xml:lang="fr">Taïwan</country><wicri:regionArea>Department of Nephrology, Chang-Gung Memorial Hospital, Keelung 204</wicri:regionArea></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="af005">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></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="2014">2014</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><title>Highlights</title><p><list list-type="simple" id="l0005"><list-item id="o0005"><label>•</label><p id="p0090">6-Mercaptopurine and 6-thioguanine are competitive inhibitors of SARS-CoV and MERS-CoV papain-like proteases.</p></list-item><list-item id="o0010"><label>•</label><p id="p0095">Mycophenolic acid can noncompetitively inhibit papain-like protease of MERS-CoV, while cannot inhibit that of SARS-CoV.</p></list-item><list-item id="o0015"><label>•</label><p id="p0100">6-Mercaptopurine/6-thioguanine and mycophenolic acid synergistically inhibit MERS-CoV papain-like protease.</p></list-item><list-item id="o0020"><label>•</label><p id="p0105">The three drugs with inhibitory effect for MERS-CoV papain-like protease can be used as lead compounds for drug 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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">25542975</article-id><article-id pub-id-type="pmc">7113672</article-id><article-id pub-id-type="publisher-id">S0166-3542(14)00362-3</article-id><article-id pub-id-type="doi">10.1016/j.antiviral.2014.12.011</article-id><article-categories><subj-group subj-group-type="heading"><subject>Article</subject></subj-group></article-categories><title-group><article-title>Thiopurine analogs and mycophenolic acid synergistically inhibit the papain-like protease of Middle East respiratory syndrome coronavirus</article-title></title-group><contrib-group><contrib contrib-type="author" id="au005"><name><surname>Cheng</surname><given-names>Kai-Wen</given-names></name><xref rid="af005" ref-type="aff">a</xref></contrib><contrib contrib-type="author" id="au010"><name><surname>Cheng</surname><given-names>Shu-Chun</given-names></name><xref rid="af010" ref-type="aff">b</xref></contrib><contrib contrib-type="author" id="au015"><name><surname>Chen</surname><given-names>Wei-Yi</given-names></name><xref rid="af015" ref-type="aff">c</xref></contrib><contrib contrib-type="author" id="au020"><name><surname>Lin</surname><given-names>Min-Han</given-names></name><xref rid="af005" ref-type="aff">a</xref></contrib><contrib contrib-type="author" id="au025"><name><surname>Chuang</surname><given-names>Shang-Ju</given-names></name><xref rid="af005" ref-type="aff">a</xref></contrib><contrib contrib-type="author" id="au030"><name><surname>Cheng</surname><given-names>I-Hsin</given-names></name><xref rid="af015" ref-type="aff">c</xref></contrib><contrib contrib-type="author" id="au035"><name><surname>Sun</surname><given-names>Chiao-Yin</given-names></name><email>fish3970@gmail.com</email><xref rid="af010" ref-type="aff">b</xref><xref rid="cor1" ref-type="corresp">⁎</xref></contrib><contrib contrib-type="author" id="au040"><name><surname>Chou</surname><given-names>Chi-Yuan</given-names></name><email>cychou@ym.edu.tw</email><xref rid="af005" ref-type="aff">a</xref><xref rid="cor1" ref-type="corresp">⁎</xref></contrib></contrib-group><aff id="af005"><label>a</label>Department of Life Sciences and Institute of Genome Sciences, National Yang-Ming University, Taipei 112, Taiwan</aff><aff id="af010"><label>b</label>Department of Nephrology, Chang-Gung Memorial Hospital, Keelung 204, Taiwan</aff><aff id="af015"><label>c</label>Institute of Biochemistry and Molecular Biology, National Yang-Ming University, Taipei 112, Taiwan</aff><author-notes><corresp id="cor1"><label>⁎</label>Corresponding authors at: 222, Mai-Chin Rd., Keelung 204, Taiwan. Tel.: +886 2 24313131x3170; fax: +886 2 24335342 (C.Y. Sun). 155 Li-Nong St., Sec. 2, Taipei 112, Taiwan. Tel.: +886 2 28267168; fax: +886 2 28202449 (C.Y. Chou). <email>fish3970@gmail.com</email><email>cychou@ym.edu.tw</email></corresp></author-notes><pub-date pub-type="pmc-release"><day>24</day><month>12</month><year>2014</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>3</month><year>2015</year></pub-date><pub-date pub-type="epub"><day>24</day><month>12</month><year>2014</year></pub-date><volume>115</volume><fpage>9</fpage><lpage>16</lpage><history><date date-type="received"><day>13</day><month>8</month><year>2014</year></date><date date-type="rev-recd"><day>8</day><month>12</month><year>2014</year></date><date date-type="accepted"><day>12</day><month>12</month><year>2014</year></date></history><permissions><copyright-statement>Copyright © 2014 Elsevier B.V. All rights reserved.</copyright-statement><copyright-year>2014</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 abstract-type="author-highlights" id="ab005"><title>Highlights</title><p><list list-type="simple" id="l0005"><list-item id="o0005"><label>•</label><p id="p0090">6-Mercaptopurine and 6-thioguanine are competitive inhibitors of SARS-CoV and MERS-CoV papain-like proteases.</p></list-item><list-item id="o0010"><label>•</label><p id="p0095">Mycophenolic acid can noncompetitively inhibit papain-like protease of MERS-CoV, while cannot inhibit that of SARS-CoV.</p></list-item><list-item id="o0015"><label>•</label><p id="p0100">6-Mercaptopurine/6-thioguanine and mycophenolic acid synergistically inhibit MERS-CoV papain-like protease.</p></list-item><list-item id="o0020"><label>•</label><p id="p0105">The three drugs with inhibitory effect for MERS-CoV papain-like protease can be used as lead compounds for drug development.</p></list-item></list></p></abstract><abstract id="ab015"><p>Middle East respiratory syndrome coronavirus (MERS-CoV) is a new highly pathogenic human coronaviruses that emerged in Jeddah and Saudi Arabia and has quickly spread to other countries in Middle East, Europe and North Africa since 2012. Up to 17 December 2014, it has infected at least 938 people with a fatality rate of about 36% globally. This has resulted in an urgent need to identify antiviral drugs that are active against MERS-CoV. The papain-like protease (PL<sup>pro</sup>) of MERS-CoV represents an important antiviral target as it is not only essential for viral maturation, but also antagonizes interferon stimulation of the host via its deubiquitination activity. Here, we report the discovery that two SARS-CoV PL<sup>pro</sup> inhibitors, 6-mercaptopurine (6MP) and 6-thioguanine (6TG), as well as the immunosuppressive drug mycophenolic acid, are able to inhibit MERS-CoV PL<sup>pro</sup>. Their inhibition mechanisms and mutually binding synergistic effect were also investigated. Our results identify for the first time three inhibitors targeting MERS-CoV PL<sup>pro</sup> and these can now be used as lead compounds for further antiviral drug development.</p></abstract><kwd-group id="kg010"><title>Abbreviations</title><kwd>AFC, 7-amino-4-trifluoro-methylcoumarin</kwd><kwd>CoV, coronavirus</kwd><kwd>DUB, deubiquitination</kwd><kwd>MERS, Middle East respiratory syndrome</kwd><kwd>6MP, 6-mercaptopurine</kwd><kwd>NEM, N-ethylmaleimide</kwd><kwd>PL<sup>pro</sup>, papain-like protease</kwd><kwd>SARS, severe acute respiratory syndrome</kwd><kwd>6TG, 6-thioguanine</kwd><kwd>Ub, ubiquitin</kwd></kwd-group><kwd-group id="kg015"><title>Keywords</title><kwd>MERS-CoV papain-like protease</kwd><kwd>6-Mercaptopurine</kwd><kwd>6-Thioguanine</kwd><kwd>Mycophenolic acid</kwd><kwd>Synergistic inhibition</kwd></kwd-group></article-meta></front></pmc></record>Pour manipuler ce document sous Unix (Dilib)
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