HIV protease inhibitor nelfinavir inhibits replication of SARS-associated coronavirus
Identifieur interne : 000E17 ( Pmc/Curation ); précédent : 000E16; suivant : 000E18HIV protease inhibitor nelfinavir inhibits replication of SARS-associated coronavirus
Auteurs : Norio Yamamoto [Japon] ; Rongge Yang [Japon] ; Yoshiyuki Yoshinaka [Japon] ; Shinji Amari [Japon] ; Tatsuya Nakano [Japon] ; Jindrich Cinatl [Allemagne] ; Holger Rabenau [Allemagne] ; Hans Wilhelm Doerr [Allemagne] ; Gerhard Hunsmann [Allemagne] ; Akira Otaka [Japon] ; Hirokazu Tamamura [Japon] ; Nobutaka Fujii [Japon] ; Naoki Yamamoto [Japon]Source :
- Biochemical and Biophysical Research Communications [ 0006-291X ] ; 2004.
Abstract
A novel coronavirus has been identified as an etiological agent of severe acute respiratory syndrome (SARS). To rapidly identify anti-SARS drugs available for clinical use, we screened a set of compounds that included antiviral drugs already in wide use. Here we report that the HIV-1 protease inhibitor, nelfinavir, strongly inhibited replication of the SARS coronavirus (SARS-CoV). Nelfinavir inhibited the cytopathic effect induced by SARS-CoV infection. Expression of viral antigens was much lower in infected cells treated with nelfinavir than in untreated infected cells. Quantitative RT-PCR analysis showed that nelfinavir could decrease the production of virions from Vero cells. Experiments with various timings of drug addition revealed that nelfinavir exerted its effect not at the entry step, but at the post-entry step of SARS-CoV infection. Our results suggest that nelfinavir should be examined clinically for the treatment of SARS and has potential as a good lead compound for designing anti-SARS drugs.
Url:
DOI: 10.1016/j.bbrc.2004.04.083
PubMed: 15144898
PubMed Central: 7111005
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xml:lang="fr">Japon</country><wicri:regionArea>Department of Molecular Virology, Bio-Response, Graduate School, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo 113-8519</wicri:regionArea></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PMC</idno><idno type="pmid">15144898</idno><idno type="pmc">7111005</idno><idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7111005</idno><idno type="RBID">PMC:7111005</idno><idno type="doi">10.1016/j.bbrc.2004.04.083</idno><date when="2004">2004</date><idno type="wicri:Area/Pmc/Corpus">000E17</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Corpus" wicri:corpus="PMC">000E17</idno><idno type="wicri:Area/Pmc/Curation">000E17</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Curation">000E17</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">HIV protease inhibitor nelfinavir inhibits replication of SARS-associated coronavirus</title><author><name sortKey="Yamamoto, Norio" sort="Yamamoto, Norio" uniqKey="Yamamoto N" first="Norio" last="Yamamoto">Norio Yamamoto</name><affiliation wicri:level="1"><nlm:aff id="AFF1">Department of Molecular Virology, Bio-Response, Graduate School, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo 113-8519, Japan</nlm:aff><country xml:lang="fr">Japon</country><wicri:regionArea>Department of Molecular Virology, Bio-Response, Graduate School, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo 113-8519</wicri:regionArea></affiliation></author><author><name sortKey="Yang, Rongge" sort="Yang, Rongge" uniqKey="Yang R" first="Rongge" last="Yang">Rongge Yang</name><affiliation wicri:level="1"><nlm:aff id="AFF1">Department of Molecular Virology, Bio-Response, Graduate School, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo 113-8519, Japan</nlm:aff><country xml:lang="fr">Japon</country><wicri:regionArea>Department of Molecular Virology, Bio-Response, Graduate School, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo 113-8519</wicri:regionArea></affiliation></author><author><name sortKey="Yoshinaka, Yoshiyuki" sort="Yoshinaka, Yoshiyuki" uniqKey="Yoshinaka Y" first="Yoshiyuki" last="Yoshinaka">Yoshiyuki Yoshinaka</name><affiliation wicri:level="1"><nlm:aff id="AFF1">Department of Molecular Virology, Bio-Response, Graduate School, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo 113-8519, Japan</nlm:aff><country xml:lang="fr">Japon</country><wicri:regionArea>Department of Molecular Virology, Bio-Response, Graduate School, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo 113-8519</wicri:regionArea></affiliation></author><author><name sortKey="Amari, Shinji" sort="Amari, Shinji" uniqKey="Amari S" first="Shinji" last="Amari">Shinji Amari</name><affiliation wicri:level="1"><nlm:aff id="AFF2">Collaborative Research Center of Frontier Simulation Software for Industrial Science, Institute of Industrial Science, University of Tokyo, 4-6-1 Komaba, Meguro-ku, Tokyo 153-8505, Japan</nlm:aff><country xml:lang="fr">Japon</country><wicri:regionArea>Collaborative Research Center of Frontier Simulation Software for Industrial Science, Institute of Industrial Science, University of Tokyo, 4-6-1 Komaba, Meguro-ku, Tokyo 153-8505</wicri:regionArea></affiliation></author><author><name sortKey="Nakano, Tatsuya" sort="Nakano, Tatsuya" uniqKey="Nakano T" first="Tatsuya" last="Nakano">Tatsuya Nakano</name><affiliation wicri:level="1"><nlm:aff id="AFF3">Division of Safety Information on Drug, Food, and Chemicals, National Institute of Health Sciences, 1-18-1 Kamiyoga, Setagaya-ku, Tokyo 158-8501, Japan</nlm:aff><country xml:lang="fr">Japon</country><wicri:regionArea>Division of Safety Information on Drug, Food, and Chemicals, National Institute of Health Sciences, 1-18-1 Kamiyoga, Setagaya-ku, Tokyo 158-8501</wicri:regionArea></affiliation></author><author><name sortKey="Cinatl, Jindrich" sort="Cinatl, Jindrich" uniqKey="Cinatl J" first="Jindrich" last="Cinatl">Jindrich Cinatl</name><affiliation wicri:level="1"><nlm:aff id="AFF4">Institute of Medical Virology, Frankfurt University Medical School, Paul-Ehrlich Str 40, D-60596 Frankfurt, Germany</nlm:aff><country xml:lang="fr">Allemagne</country><wicri:regionArea>Institute of Medical Virology, Frankfurt University Medical School, Paul-Ehrlich Str 40, D-60596 Frankfurt</wicri:regionArea></affiliation></author><author><name sortKey="Rabenau, Holger" sort="Rabenau, Holger" uniqKey="Rabenau H" first="Holger" last="Rabenau">Holger Rabenau</name><affiliation wicri:level="1"><nlm:aff id="AFF4">Institute of Medical Virology, Frankfurt University Medical School, Paul-Ehrlich Str 40, D-60596 Frankfurt, Germany</nlm:aff><country xml:lang="fr">Allemagne</country><wicri:regionArea>Institute of Medical Virology, Frankfurt University Medical School, Paul-Ehrlich Str 40, D-60596 Frankfurt</wicri:regionArea></affiliation></author><author><name sortKey="Doerr, Hans Wilhelm" sort="Doerr, Hans Wilhelm" uniqKey="Doerr H" first="Hans Wilhelm" last="Doerr">Hans Wilhelm Doerr</name><affiliation wicri:level="1"><nlm:aff id="AFF4">Institute of Medical Virology, Frankfurt University Medical School, Paul-Ehrlich Str 40, D-60596 Frankfurt, Germany</nlm:aff><country xml:lang="fr">Allemagne</country><wicri:regionArea>Institute of Medical Virology, Frankfurt University Medical School, Paul-Ehrlich Str 40, D-60596 Frankfurt</wicri:regionArea></affiliation></author><author><name sortKey="Hunsmann, Gerhard" sort="Hunsmann, Gerhard" uniqKey="Hunsmann G" first="Gerhard" last="Hunsmann">Gerhard Hunsmann</name><affiliation wicri:level="1"><nlm:aff id="AFF5">Department of Virology and Immunology, German Primate Center, Kellnerweg 4, D-37077 Gottingen, Germany</nlm:aff><country xml:lang="fr">Allemagne</country><wicri:regionArea>Department of Virology and Immunology, German Primate Center, Kellnerweg 4, D-37077 Gottingen</wicri:regionArea></affiliation></author><author><name sortKey="Otaka, Akira" sort="Otaka, Akira" uniqKey="Otaka A" first="Akira" last="Otaka">Akira Otaka</name><affiliation wicri:level="1"><nlm:aff id="AFF6">Graduate School of Pharmaceutical Sciences, Kyoto University, Sakyo-ku, Kyoto 606-8501, Japan</nlm:aff><country xml:lang="fr">Japon</country><wicri:regionArea>Graduate School of Pharmaceutical Sciences, Kyoto University, Sakyo-ku, Kyoto 606-8501</wicri:regionArea></affiliation></author><author><name sortKey="Tamamura, Hirokazu" sort="Tamamura, Hirokazu" uniqKey="Tamamura H" first="Hirokazu" last="Tamamura">Hirokazu Tamamura</name><affiliation wicri:level="1"><nlm:aff id="AFF6">Graduate School of Pharmaceutical Sciences, Kyoto University, Sakyo-ku, Kyoto 606-8501, Japan</nlm:aff><country xml:lang="fr">Japon</country><wicri:regionArea>Graduate School of Pharmaceutical Sciences, Kyoto University, Sakyo-ku, Kyoto 606-8501</wicri:regionArea></affiliation></author><author><name sortKey="Fujii, Nobutaka" sort="Fujii, Nobutaka" uniqKey="Fujii N" first="Nobutaka" last="Fujii">Nobutaka Fujii</name><affiliation wicri:level="1"><nlm:aff id="AFF6">Graduate School of Pharmaceutical Sciences, Kyoto University, Sakyo-ku, Kyoto 606-8501, Japan</nlm:aff><country xml:lang="fr">Japon</country><wicri:regionArea>Graduate School of Pharmaceutical Sciences, Kyoto University, Sakyo-ku, Kyoto 606-8501</wicri:regionArea></affiliation></author><author><name sortKey="Yamamoto, Naoki" sort="Yamamoto, Naoki" uniqKey="Yamamoto N" first="Naoki" last="Yamamoto">Naoki Yamamoto</name><affiliation wicri:level="1"><nlm:aff id="AFF1">Department of Molecular Virology, Bio-Response, Graduate School, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo 113-8519, Japan</nlm:aff><country xml:lang="fr">Japon</country><wicri:regionArea>Department of Molecular Virology, Bio-Response, Graduate School, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo 113-8519</wicri:regionArea></affiliation></author></analytic><series><title level="j">Biochemical and Biophysical Research Communications</title><idno type="ISSN">0006-291X</idno><idno type="eISSN">1090-2104</idno><imprint><date when="2004">2004</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><p>A novel coronavirus has been identified as an etiological agent of severe acute respiratory syndrome (SARS). To rapidly identify anti-SARS drugs available for clinical use, we screened a set of compounds that included antiviral drugs already in wide use. Here we report that the HIV-1 protease inhibitor, nelfinavir, strongly inhibited replication of the SARS coronavirus (SARS-CoV). Nelfinavir inhibited the cytopathic effect induced by SARS-CoV infection. Expression of viral antigens was much lower in infected cells treated with nelfinavir than in untreated infected cells. Quantitative RT-PCR analysis showed that nelfinavir could decrease the production of virions from Vero cells. Experiments with various timings of drug addition revealed that nelfinavir exerted its effect not at the entry step, but at the post-entry step of SARS-CoV infection. Our results suggest that nelfinavir should be examined clinically for the treatment of SARS and has potential as a good lead compound for designing anti-SARS drugs.</p></div></front><back><div1 type="bibliography"><listBibl><biblStruct><analytic><author><name sortKey="Lee, N" uniqKey="Lee N">N Lee</name></author><author><name sortKey="Hui, D" uniqKey="Hui D">D Hui</name></author><author><name sortKey="Wu, A" uniqKey="Wu A">A Wu</name></author><author><name sortKey="Chan, P" uniqKey="Chan P">P Chan</name></author><author><name sortKey="Cameron, P" uniqKey="Cameron P">P Cameron</name></author><author><name sortKey="Joynt, G M" uniqKey="Joynt G">G.M Joynt</name></author><author><name sortKey="Ahuja, A" uniqKey="Ahuja A">A Ahuja</name></author><author><name sortKey="Yung, M Y" uniqKey="Yung M">M.Y Yung</name></author><author><name sortKey="Leung, C B" uniqKey="Leung C">C.B Leung</name></author><author><name sortKey="To, K F" uniqKey="To K">K.F To</name></author><author><name sortKey="Lui, 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<front><journal-meta><journal-id journal-id-type="nlm-ta">Biochem Biophys Res Commun</journal-id><journal-id journal-id-type="iso-abbrev">Biochem. Biophys. Res. Commun</journal-id><journal-title-group><journal-title>Biochemical and Biophysical Research Communications</journal-title></journal-title-group><issn pub-type="ppub">0006-291X</issn><issn pub-type="epub">1090-2104</issn><publisher><publisher-name>Elsevier Inc.</publisher-name></publisher></journal-meta><article-meta><article-id pub-id-type="pmid">15144898</article-id><article-id pub-id-type="pmc">7111005</article-id><article-id pub-id-type="publisher-id">S0006-291X(04)00815-0</article-id><article-id pub-id-type="doi">10.1016/j.bbrc.2004.04.083</article-id><article-categories><subj-group subj-group-type="heading"><subject>Article</subject></subj-group></article-categories><title-group><article-title>HIV protease inhibitor nelfinavir inhibits replication of SARS-associated coronavirus</article-title></title-group><contrib-group><contrib contrib-type="author"><name><surname>Yamamoto</surname><given-names>Norio</given-names></name><xref rid="AFF1" ref-type="aff">a</xref></contrib><contrib contrib-type="author"><name><surname>Yang</surname><given-names>Rongge</given-names></name><xref rid="AFF1" ref-type="aff">a</xref></contrib><contrib contrib-type="author"><name><surname>Yoshinaka</surname><given-names>Yoshiyuki</given-names></name><xref rid="AFF1" ref-type="aff">a</xref></contrib><contrib contrib-type="author"><name><surname>Amari</surname><given-names>Shinji</given-names></name><xref rid="AFF2" ref-type="aff">b</xref></contrib><contrib contrib-type="author"><name><surname>Nakano</surname><given-names>Tatsuya</given-names></name><xref rid="AFF3" ref-type="aff">c</xref></contrib><contrib contrib-type="author"><name><surname>Cinatl</surname><given-names>Jindrich</given-names></name><xref rid="AFF4" ref-type="aff">d</xref></contrib><contrib contrib-type="author"><name><surname>Rabenau</surname><given-names>Holger</given-names></name><xref rid="AFF4" ref-type="aff">d</xref></contrib><contrib contrib-type="author"><name><surname>Doerr</surname><given-names>Hans Wilhelm</given-names></name><xref rid="AFF4" ref-type="aff">d</xref></contrib><contrib contrib-type="author"><name><surname>Hunsmann</surname><given-names>Gerhard</given-names></name><xref rid="AFF5" ref-type="aff">e</xref></contrib><contrib contrib-type="author"><name><surname>Otaka</surname><given-names>Akira</given-names></name><xref rid="AFF6" ref-type="aff">f</xref></contrib><contrib contrib-type="author"><name><surname>Tamamura</surname><given-names>Hirokazu</given-names></name><xref rid="AFF6" ref-type="aff">f</xref></contrib><contrib contrib-type="author"><name><surname>Fujii</surname><given-names>Nobutaka</given-names></name><xref rid="AFF6" ref-type="aff">f</xref></contrib><contrib contrib-type="author"><name><surname>Yamamoto</surname><given-names>Naoki</given-names></name><email>yamamoto.mmb@tmd.ac.jp</email><xref rid="AFF1" ref-type="aff">a</xref><xref rid="COR1" ref-type="corresp">∗</xref></contrib></contrib-group><aff id="AFF1"><label>a</label>Department of Molecular Virology, Bio-Response, Graduate School, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo 113-8519, Japan</aff><aff id="AFF2"><label>b</label>Collaborative Research Center of Frontier Simulation Software for Industrial Science, Institute of Industrial Science, University of Tokyo, 4-6-1 Komaba, Meguro-ku, Tokyo 153-8505, Japan</aff><aff id="AFF3"><label>c</label>Division of Safety Information on Drug, Food, and Chemicals, National Institute of Health Sciences, 1-18-1 Kamiyoga, Setagaya-ku, Tokyo 158-8501, Japan</aff><aff id="AFF4"><label>d</label>Institute of Medical Virology, Frankfurt University Medical School, Paul-Ehrlich Str 40, D-60596 Frankfurt, Germany</aff><aff id="AFF5"><label>e</label>Department of Virology and Immunology, German Primate Center, Kellnerweg 4, D-37077 Gottingen, Germany</aff><aff id="AFF6"><label>f</label>Graduate School of Pharmaceutical Sciences, Kyoto University, Sakyo-ku, Kyoto 606-8501, Japan</aff><author-notes><corresp id="COR1"><label>∗</label>Corresponding author. Fax: +81-3-5803-0124 <email>yamamoto.mmb@tmd.ac.jp</email></corresp></author-notes><pub-date pub-type="pmc-release"><day>6</day><month>5</month><year>2004</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"><day>4</day><month>6</month><year>2004</year></pub-date><pub-date pub-type="epub"><day>6</day><month>5</month><year>2004</year></pub-date><volume>318</volume><issue>3</issue><fpage>719</fpage><lpage>725</lpage><history><date date-type="received"><day>7</day><month>4</month><year>2004</year></date></history><permissions><copyright-statement>Copyright © 2004 Elsevier Inc. All rights reserved.</copyright-statement><copyright-year>2004</copyright-year><copyright-holder>Elsevier Inc.</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><p>A novel coronavirus has been identified as an etiological agent of severe acute respiratory syndrome (SARS). To rapidly identify anti-SARS drugs available for clinical use, we screened a set of compounds that included antiviral drugs already in wide use. Here we report that the HIV-1 protease inhibitor, nelfinavir, strongly inhibited replication of the SARS coronavirus (SARS-CoV). Nelfinavir inhibited the cytopathic effect induced by SARS-CoV infection. Expression of viral antigens was much lower in infected cells treated with nelfinavir than in untreated infected cells. Quantitative RT-PCR analysis showed that nelfinavir could decrease the production of virions from Vero cells. Experiments with various timings of drug addition revealed that nelfinavir exerted its effect not at the entry step, but at the post-entry step of SARS-CoV infection. Our results suggest that nelfinavir should be examined clinically for the treatment of SARS and has potential as a good lead compound for designing anti-SARS drugs.</p></abstract><kwd-group><title>Keywords</title><kwd>Severe acute respiratory syndrome</kwd><kwd>Coronavirus</kwd><kwd>HIV protease inhibitor</kwd></kwd-group></article-meta></front></pmc></record>Pour manipuler ce document sous Unix (Dilib)
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