Structure-Based Design, Synthesis, and Biological Evaluation of a Series of Novel and Reversible Inhibitors for the Severe Acute Respiratory Syndrome-Coronavirus Papain-Like Protease
Identifieur interne : 000183 ( PascalFrancis/Checkpoint ); précédent : 000182; suivant : 000184Structure-Based Design, Synthesis, and Biological Evaluation of a Series of Novel and Reversible Inhibitors for the Severe Acute Respiratory Syndrome-Coronavirus Papain-Like Protease
Auteurs : Arun K. Ghosh [États-Unis] ; Jun Takayama [États-Unis] ; Yoann Aubin [États-Unis] ; Kiira Ratia [États-Unis] ; Rima Chaudhuri [États-Unis] ; Yahira Baez [États-Unis] ; Katrina Sleeman [États-Unis] ; Melissa Coughlin [États-Unis] ; Daniel B. Nichols [États-Unis] ; Debbie C. Mulhearn [États-Unis] ; Bellur S. Prabhakar [États-Unis] ; Susan C. Bakery [États-Unis] ; Michael E. Johnson [États-Unis] ; Andrew D. Mesecar [États-Unis]Source :
- Journal of medicinal chemistry : (Print) [ 0022-2623 ] ; 2009.
Descripteurs français
- Pascal (Inist)
- Relation structure activité, Synthèse chimique, Antiviral, Cysteine endopeptidases, Virus syndrome respiratoire aigu sévère, Composé non peptide, Inhibiteur enzyme, Dérivé du benzène, Dérivé du naphtalène, Amine secondaire, Carboxamide, In vitro, Modèle moléculaire, Complexe enzyme inhibiteur, Modélisation, Benzamide(2-méthyl-5-méthylamino-N-[1-(1-naphtyl)éthyl]).
English descriptors
- KwdEn :
- Antiviral, Benzene derivatives, Carboxamide, Chemical synthesis, Cysteine endopeptidases, Enzyme inhibitor, In vitro, Inhibitor enzyme complex, Modeling, Molecular model, Naphthalene derivatives, Non peptide compound, Secondary amine, Severe acute respiratory syndrome virus, Structure activity relation.
Abstract
We describe here the design, synthesis, molecular modeling, and biological evaluation of a series of small molecule, nonpeptide inhibitors of SARS-CoV PLpro. Our initial lead compound was identified via high-throughput screening of a diverse chemical library. We subsequently carried out structure-activity relationship studies and optimized the lead structure to potent inhibitors that have shown antiviral activity against SARS-CoV infected Vero E6 cells. Upon the basis of the X-ray crystal structure of inhibitor 24-bound to SARS-CoV PLpro, a drug design template was created. Our structure-based modification led to the design of a more potent inhibitor, 2 (enzyme IC50 = 0.46 μM; antiviral EC50 = 6 μM). Interestingly, its methylamine derivative, 49, displayed good enzyme inhibitory potency (IC50 = 1.3 uM) and the most potent SARS antiviral activity (EC50 = 5.2 μM) in the series. We have carried out computational docking studies and generated a predictive 3D-QSAR model for SARS-CoV PLpro inhibitors.
Affiliations:
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Pascal:09-0461730Le document en format XML
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<sourceDesc><biblStruct><analytic><title xml:lang="en" level="a">Structure-Based Design, Synthesis, and Biological Evaluation of a Series of Novel and Reversible Inhibitors for the Severe Acute Respiratory Syndrome-Coronavirus Papain-Like Protease</title>
<author><name sortKey="Ghosh, Arun K" sort="Ghosh, Arun K" uniqKey="Ghosh A" first="Arun K." last="Ghosh">Arun K. Ghosh</name>
<affiliation wicri:level="1"><inist:fA14 i1="01"><s1>Departments of Chemistry and Medicinal Chemistry, Purdue University, 560 Oval Drive</s1>
<s2>West Lafayette, Indiana 47907</s2>
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<wicri:noRegion>West Lafayette, Indiana 47907</wicri:noRegion>
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</author>
<author><name sortKey="Takayama, Jun" sort="Takayama, Jun" uniqKey="Takayama J" first="Jun" last="Takayama">Jun Takayama</name>
<affiliation wicri:level="1"><inist:fA14 i1="01"><s1>Departments of Chemistry and Medicinal Chemistry, Purdue University, 560 Oval Drive</s1>
<s2>West Lafayette, Indiana 47907</s2>
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<author><name sortKey="Aubin, Yoann" sort="Aubin, Yoann" uniqKey="Aubin Y" first="Yoann" last="Aubin">Yoann Aubin</name>
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<author><name sortKey="Ratia, Kiira" sort="Ratia, Kiira" uniqKey="Ratia K" first="Kiira" last="Ratia">Kiira Ratia</name>
<affiliation wicri:level="4"><inist:fA14 i1="02"><s1>Center for Pharmaceutical Biotechnology and Department of Medicinal Chemistry and Pharmacognosy, University of Illinois at Chicago, 900 South Ashland Avenue</s1>
<s2>Chicago, Illinois 60607</s2>
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<author><name sortKey="Chaudhuri, Rima" sort="Chaudhuri, Rima" uniqKey="Chaudhuri R" first="Rima" last="Chaudhuri">Rima Chaudhuri</name>
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<author><name sortKey="Sleeman, Katrina" sort="Sleeman, Katrina" uniqKey="Sleeman K" first="Katrina" last="Sleeman">Katrina Sleeman</name>
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<author><name sortKey="Coughlin, Melissa" sort="Coughlin, Melissa" uniqKey="Coughlin M" first="Melissa" last="Coughlin">Melissa Coughlin</name>
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<author><name sortKey="Mulhearn, Debbie C" sort="Mulhearn, Debbie C" uniqKey="Mulhearn D" first="Debbie C." last="Mulhearn">Debbie C. Mulhearn</name>
<affiliation wicri:level="4"><inist:fA14 i1="02"><s1>Center for Pharmaceutical Biotechnology and Department of Medicinal Chemistry and Pharmacognosy, University of Illinois at Chicago, 900 South Ashland Avenue</s1>
<s2>Chicago, Illinois 60607</s2>
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<placeName><settlement type="city">Chicago</settlement>
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<author><name sortKey="Prabhakar, Bellur S" sort="Prabhakar, Bellur S" uniqKey="Prabhakar B" first="Bellur S." last="Prabhakar">Bellur S. Prabhakar</name>
<affiliation wicri:level="1"><inist:fA14 i1="04"><s1>Department of Microbiology and Immunology, University of lllinois</s1>
<s2>Chicago, Illinois 60607</s2>
<s3>USA</s3>
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</author>
<author><name sortKey="Bakery, Susan C" sort="Bakery, Susan C" uniqKey="Bakery S" first="Susan C." last="Bakery">Susan C. Bakery</name>
<affiliation wicri:level="4"><inist:fA14 i1="03"><s1>Department of Microbiology and Immunology, Loyola University of Chicago, Stritch School of Medicine</s1>
<s2>Maywood, Illinois 60153</s2>
<s3>USA</s3>
<sZ>7 aut.</sZ>
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<sZ>12 aut.</sZ>
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<wicri:noRegion>Maywood, Illinois 60153</wicri:noRegion>
<orgName type="university">Université de Chicago</orgName>
<placeName><settlement type="city">Chicago</settlement>
<region type="state">Illinois</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Johnson, Michael E" sort="Johnson, Michael E" uniqKey="Johnson M" first="Michael E." last="Johnson">Michael E. Johnson</name>
<affiliation wicri:level="4"><inist:fA14 i1="02"><s1>Center for Pharmaceutical Biotechnology and Department of Medicinal Chemistry and Pharmacognosy, University of Illinois at Chicago, 900 South Ashland Avenue</s1>
<s2>Chicago, Illinois 60607</s2>
<s3>USA</s3>
<sZ>4 aut.</sZ>
<sZ>6 aut.</sZ>
<sZ>10 aut.</sZ>
<sZ>13 aut.</sZ>
<sZ>14 aut.</sZ>
</inist:fA14>
<country>États-Unis</country>
<wicri:noRegion>Chicago, Illinois 60607</wicri:noRegion>
<orgName type="university">Université de l'Illinois à Chicago</orgName>
<placeName><settlement type="city">Chicago</settlement>
<region type="state">Illinois</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Mesecar, Andrew D" sort="Mesecar, Andrew D" uniqKey="Mesecar A" first="Andrew D." last="Mesecar">Andrew D. Mesecar</name>
<affiliation wicri:level="4"><inist:fA14 i1="02"><s1>Center for Pharmaceutical Biotechnology and Department of Medicinal Chemistry and Pharmacognosy, University of Illinois at Chicago, 900 South Ashland Avenue</s1>
<s2>Chicago, Illinois 60607</s2>
<s3>USA</s3>
<sZ>4 aut.</sZ>
<sZ>6 aut.</sZ>
<sZ>10 aut.</sZ>
<sZ>13 aut.</sZ>
<sZ>14 aut.</sZ>
</inist:fA14>
<country>États-Unis</country>
<wicri:noRegion>Chicago, Illinois 60607</wicri:noRegion>
<orgName type="university">Université de l'Illinois à Chicago</orgName>
<placeName><settlement type="city">Chicago</settlement>
<region type="state">Illinois</region>
</placeName>
</affiliation>
</author>
</analytic>
<series><title level="j" type="main">Journal of medicinal chemistry : (Print)</title>
<title level="j" type="abbreviated">J. med. chem. : (Print)</title>
<idno type="ISSN">0022-2623</idno>
<imprint><date when="2009">2009</date>
</imprint>
</series>
</biblStruct>
</sourceDesc>
<seriesStmt><title level="j" type="main">Journal of medicinal chemistry : (Print)</title>
<title level="j" type="abbreviated">J. med. chem. : (Print)</title>
<idno type="ISSN">0022-2623</idno>
</seriesStmt>
</fileDesc>
<profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Antiviral</term>
<term>Benzene derivatives</term>
<term>Carboxamide</term>
<term>Chemical synthesis</term>
<term>Cysteine endopeptidases</term>
<term>Enzyme inhibitor</term>
<term>In vitro</term>
<term>Inhibitor enzyme complex</term>
<term>Modeling</term>
<term>Molecular model</term>
<term>Naphthalene derivatives</term>
<term>Non peptide compound</term>
<term>Secondary amine</term>
<term>Severe acute respiratory syndrome virus</term>
<term>Structure activity relation</term>
</keywords>
<keywords scheme="Pascal" xml:lang="fr"><term>Relation structure activité</term>
<term>Synthèse chimique</term>
<term>Antiviral</term>
<term>Cysteine endopeptidases</term>
<term>Virus syndrome respiratoire aigu sévère</term>
<term>Composé non peptide</term>
<term>Inhibiteur enzyme</term>
<term>Dérivé du benzène</term>
<term>Dérivé du naphtalène</term>
<term>Amine secondaire</term>
<term>Carboxamide</term>
<term>In vitro</term>
<term>Modèle moléculaire</term>
<term>Complexe enzyme inhibiteur</term>
<term>Modélisation</term>
<term>Benzamide(2-méthyl-5-méthylamino-N-[1-(1-naphtyl)éthyl])</term>
</keywords>
</textClass>
</profileDesc>
</teiHeader>
<front><div type="abstract" xml:lang="en">We describe here the design, synthesis, molecular modeling, and biological evaluation of a series of small molecule, nonpeptide inhibitors of SARS-CoV PLpro. Our initial lead compound was identified via high-throughput screening of a diverse chemical library. We subsequently carried out structure-activity relationship studies and optimized the lead structure to potent inhibitors that have shown antiviral activity against SARS-CoV infected Vero E6 cells. Upon the basis of the X-ray crystal structure of inhibitor 24-bound to SARS-CoV PLpro, a drug design template was created. Our structure-based modification led to the design of a more potent inhibitor, 2 (enzyme IC<sub>50</sub>
= 0.46 μM; antiviral EC<sub>50</sub>
= 6 μM). Interestingly, its methylamine derivative, 49, displayed good enzyme inhibitory potency (IC<sub>50</sub>
= 1.3 uM) and the most potent SARS antiviral activity (EC<sub>50</sub>
= 5.2 μM) in the series. We have carried out computational docking studies and generated a predictive 3D-QSAR model for SARS-CoV PLpro inhibitors.</div>
</front>
</TEI>
<inist><standard h6="B"><pA><fA01 i1="01" i2="1"><s0>0022-2623</s0>
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<fA03 i2="1"><s0>J. med. chem. : (Print)</s0>
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<fA05><s2>52</s2>
</fA05>
<fA06><s2>16</s2>
</fA06>
<fA08 i1="01" i2="1" l="ENG"><s1>Structure-Based Design, Synthesis, and Biological Evaluation of a Series of Novel and Reversible Inhibitors for the Severe Acute Respiratory Syndrome-Coronavirus Papain-Like Protease</s1>
</fA08>
<fA11 i1="01" i2="1"><s1>GHOSH (Arun K.)</s1>
</fA11>
<fA11 i1="02" i2="1"><s1>TAKAYAMA (Jun)</s1>
</fA11>
<fA11 i1="03" i2="1"><s1>AUBIN (Yoann)</s1>
</fA11>
<fA11 i1="04" i2="1"><s1>RATIA (Kiira)</s1>
</fA11>
<fA11 i1="05" i2="1"><s1>CHAUDHURI (Rima)</s1>
</fA11>
<fA11 i1="06" i2="1"><s1>BAEZ (Yahira)</s1>
</fA11>
<fA11 i1="07" i2="1"><s1>SLEEMAN (Katrina)</s1>
</fA11>
<fA11 i1="08" i2="1"><s1>COUGHLIN (Melissa)</s1>
</fA11>
<fA11 i1="09" i2="1"><s1>NICHOLS (Daniel B.)</s1>
</fA11>
<fA11 i1="10" i2="1"><s1>MULHEARN (Debbie C.)</s1>
</fA11>
<fA11 i1="11" i2="1"><s1>PRABHAKAR (Bellur S.)</s1>
</fA11>
<fA11 i1="12" i2="1"><s1>BAKERY (Susan C.)</s1>
</fA11>
<fA11 i1="13" i2="1"><s1>JOHNSON (Michael E.)</s1>
</fA11>
<fA11 i1="14" i2="1"><s1>MESECAR (Andrew D.)</s1>
</fA11>
<fA14 i1="01"><s1>Departments of Chemistry and Medicinal Chemistry, Purdue University, 560 Oval Drive</s1>
<s2>West Lafayette, Indiana 47907</s2>
<s3>USA</s3>
<sZ>1 aut.</sZ>
<sZ>2 aut.</sZ>
<sZ>3 aut.</sZ>
<sZ>5 aut.</sZ>
</fA14>
<fA14 i1="02"><s1>Center for Pharmaceutical Biotechnology and Department of Medicinal Chemistry and Pharmacognosy, University of Illinois at Chicago, 900 South Ashland Avenue</s1>
<s2>Chicago, Illinois 60607</s2>
<s3>USA</s3>
<sZ>4 aut.</sZ>
<sZ>6 aut.</sZ>
<sZ>10 aut.</sZ>
<sZ>13 aut.</sZ>
<sZ>14 aut.</sZ>
</fA14>
<fA14 i1="03"><s1>Department of Microbiology and Immunology, Loyola University of Chicago, Stritch School of Medicine</s1>
<s2>Maywood, Illinois 60153</s2>
<s3>USA</s3>
<sZ>7 aut.</sZ>
<sZ>9 aut.</sZ>
<sZ>12 aut.</sZ>
</fA14>
<fA14 i1="04"><s1>Department of Microbiology and Immunology, University of lllinois</s1>
<s2>Chicago, Illinois 60607</s2>
<s3>USA</s3>
<sZ>8 aut.</sZ>
<sZ>11 aut.</sZ>
</fA14>
<fA20><s1>5228-5240</s1>
</fA20>
<fA21><s1>2009</s1>
</fA21>
<fA23 i1="01"><s0>ENG</s0>
</fA23>
<fA43 i1="01"><s1>INIST</s1>
<s2>9165</s2>
<s5>354000187649290240</s5>
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<fA44><s0>0000</s0>
<s1>© 2009 INIST-CNRS. All rights reserved.</s1>
</fA44>
<fA45><s0>26 ref.</s0>
</fA45>
<fA47 i1="01" i2="1"><s0>09-0461730</s0>
</fA47>
<fA60><s1>P</s1>
</fA60>
<fA61><s0>A</s0>
</fA61>
<fA64 i1="01" i2="1"><s0>Journal of medicinal chemistry : (Print)</s0>
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<fA66 i1="01"><s0>USA</s0>
</fA66>
<fC01 i1="01" l="ENG"><s0>We describe here the design, synthesis, molecular modeling, and biological evaluation of a series of small molecule, nonpeptide inhibitors of SARS-CoV PLpro. Our initial lead compound was identified via high-throughput screening of a diverse chemical library. We subsequently carried out structure-activity relationship studies and optimized the lead structure to potent inhibitors that have shown antiviral activity against SARS-CoV infected Vero E6 cells. Upon the basis of the X-ray crystal structure of inhibitor 24-bound to SARS-CoV PLpro, a drug design template was created. Our structure-based modification led to the design of a more potent inhibitor, 2 (enzyme IC<sub>50</sub>
= 0.46 μM; antiviral EC<sub>50</sub>
= 6 μM). Interestingly, its methylamine derivative, 49, displayed good enzyme inhibitory potency (IC<sub>50</sub>
= 1.3 uM) and the most potent SARS antiviral activity (EC<sub>50</sub>
= 5.2 μM) in the series. We have carried out computational docking studies and generated a predictive 3D-QSAR model for SARS-CoV PLpro inhibitors.</s0>
</fC01>
<fC02 i1="01" i2="X"><s0>002B02S05</s0>
</fC02>
<fC03 i1="01" i2="X" l="FRE"><s0>Relation structure activité</s0>
<s5>01</s5>
</fC03>
<fC03 i1="01" i2="X" l="ENG"><s0>Structure activity relation</s0>
<s5>01</s5>
</fC03>
<fC03 i1="01" i2="X" l="SPA"><s0>Relación estructura actividad</s0>
<s5>01</s5>
</fC03>
<fC03 i1="02" i2="X" l="FRE"><s0>Synthèse chimique</s0>
<s5>02</s5>
</fC03>
<fC03 i1="02" i2="X" l="ENG"><s0>Chemical synthesis</s0>
<s5>02</s5>
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<s5>02</s5>
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<s5>03</s5>
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<s5>03</s5>
</fC03>
<fC03 i1="03" i2="X" l="SPA"><s0>Antiviral</s0>
<s5>03</s5>
</fC03>
<fC03 i1="04" i2="X" l="FRE"><s0>Cysteine endopeptidases</s0>
<s2>FE</s2>
<s5>04</s5>
</fC03>
<fC03 i1="04" i2="X" l="ENG"><s0>Cysteine endopeptidases</s0>
<s2>FE</s2>
<s5>04</s5>
</fC03>
<fC03 i1="04" i2="X" l="SPA"><s0>Cysteine endopeptidases</s0>
<s2>FE</s2>
<s5>04</s5>
</fC03>
<fC03 i1="05" i2="X" l="FRE"><s0>Virus syndrome respiratoire aigu sévère</s0>
<s2>NW</s2>
<s5>05</s5>
</fC03>
<fC03 i1="05" i2="X" l="ENG"><s0>Severe acute respiratory syndrome virus</s0>
<s2>NW</s2>
<s5>05</s5>
</fC03>
<fC03 i1="05" i2="X" l="SPA"><s0>Severe acute respiratory syndrome virus</s0>
<s2>NW</s2>
<s5>05</s5>
</fC03>
<fC03 i1="06" i2="X" l="FRE"><s0>Composé non peptide</s0>
<s5>06</s5>
</fC03>
<fC03 i1="06" i2="X" l="ENG"><s0>Non peptide compound</s0>
<s5>06</s5>
</fC03>
<fC03 i1="06" i2="X" l="SPA"><s0>Compuesto no péptido</s0>
<s5>06</s5>
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<fC03 i1="07" i2="X" l="FRE"><s0>Inhibiteur enzyme</s0>
<s5>07</s5>
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<s5>07</s5>
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<s5>07</s5>
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<s5>08</s5>
</fC03>
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<s5>08</s5>
</fC03>
<fC03 i1="08" i2="X" l="SPA"><s0>Benceno derivado</s0>
<s5>08</s5>
</fC03>
<fC03 i1="09" i2="X" l="FRE"><s0>Dérivé du naphtalène</s0>
<s5>09</s5>
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<fC03 i1="09" i2="X" l="ENG"><s0>Naphthalene derivatives</s0>
<s5>09</s5>
</fC03>
<fC03 i1="09" i2="X" l="SPA"><s0>Naftaleno derivado</s0>
<s5>09</s5>
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<fC03 i1="10" i2="X" l="FRE"><s0>Amine secondaire</s0>
<s5>10</s5>
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<s5>10</s5>
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<s5>10</s5>
</fC03>
<fC03 i1="11" i2="X" l="FRE"><s0>Carboxamide</s0>
<s5>11</s5>
</fC03>
<fC03 i1="11" i2="X" l="ENG"><s0>Carboxamide</s0>
<s5>11</s5>
</fC03>
<fC03 i1="11" i2="X" l="SPA"><s0>Carboxamida</s0>
<s5>11</s5>
</fC03>
<fC03 i1="12" i2="X" l="FRE"><s0>In vitro</s0>
<s5>12</s5>
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<fC03 i1="12" i2="X" l="ENG"><s0>In vitro</s0>
<s5>12</s5>
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<fC03 i1="12" i2="X" l="SPA"><s0>In vitro</s0>
<s5>12</s5>
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<fC03 i1="13" i2="X" l="FRE"><s0>Modèle moléculaire</s0>
<s5>13</s5>
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<s5>13</s5>
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<fC03 i1="13" i2="X" l="SPA"><s0>Modelo molecular</s0>
<s5>13</s5>
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<fC03 i1="14" i2="X" l="FRE"><s0>Complexe enzyme inhibiteur</s0>
<s5>14</s5>
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<fC03 i1="14" i2="X" l="ENG"><s0>Inhibitor enzyme complex</s0>
<s5>14</s5>
</fC03>
<fC03 i1="14" i2="X" l="SPA"><s0>Complejo enzima inhibidor</s0>
<s5>14</s5>
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<fC03 i1="15" i2="X" l="FRE"><s0>Modélisation</s0>
<s5>32</s5>
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<fC03 i1="15" i2="X" l="ENG"><s0>Modeling</s0>
<s5>32</s5>
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<fC03 i1="15" i2="X" l="SPA"><s0>Modelización</s0>
<s5>32</s5>
</fC03>
<fC03 i1="16" i2="X" l="FRE"><s0>Benzamide(2-méthyl-5-méthylamino-N-[1-(1-naphtyl)éthyl])</s0>
<s2>NK</s2>
<s2>FR</s2>
<s4>INC</s4>
<s5>76</s5>
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<fC07 i1="01" i2="X" l="FRE"><s0>Peptidases</s0>
<s2>FE</s2>
</fC07>
<fC07 i1="01" i2="X" l="ENG"><s0>Peptidases</s0>
<s2>FE</s2>
</fC07>
<fC07 i1="01" i2="X" l="SPA"><s0>Peptidases</s0>
<s2>FE</s2>
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<s2>FE</s2>
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<s2>FE</s2>
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<fC07 i1="03" i2="X" l="FRE"><s0>Enzyme</s0>
<s2>FE</s2>
</fC07>
<fC07 i1="03" i2="X" l="ENG"><s0>Enzyme</s0>
<s2>FE</s2>
</fC07>
<fC07 i1="03" i2="X" l="SPA"><s0>Enzima</s0>
<s2>FE</s2>
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<fC07 i1="04" i2="X" l="FRE"><s0>Coronavirus</s0>
<s2>NW</s2>
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<fC07 i1="04" i2="X" l="ENG"><s0>Coronavirus</s0>
<s2>NW</s2>
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<fC07 i1="04" i2="X" l="SPA"><s0>Coronavirus</s0>
<s2>NW</s2>
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<fC07 i1="05" i2="X" l="FRE"><s0>Coronaviridae</s0>
<s2>NW</s2>
</fC07>
<fC07 i1="05" i2="X" l="ENG"><s0>Coronaviridae</s0>
<s2>NW</s2>
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<fC07 i1="05" i2="X" l="SPA"><s0>Coronaviridae</s0>
<s2>NW</s2>
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<s2>NW</s2>
</fC07>
<fC07 i1="06" i2="X" l="ENG"><s0>Nidovirales</s0>
<s2>NW</s2>
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<fC07 i1="06" i2="X" l="SPA"><s0>Nidovirales</s0>
<s2>NW</s2>
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<fC07 i1="07" i2="X" l="FRE"><s0>Virus</s0>
<s2>NW</s2>
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<s2>NW</s2>
</fC07>
<fC07 i1="07" i2="X" l="SPA"><s0>Virus</s0>
<s2>NW</s2>
</fC07>
<fN21><s1>334</s1>
</fN21>
</pA>
</standard>
</inist>
<affiliations><list><country><li>États-Unis</li>
</country>
<region><li>Illinois</li>
</region>
<settlement><li>Chicago</li>
</settlement>
<orgName><li>Université de Chicago</li>
<li>Université de l'Illinois à Chicago</li>
</orgName>
</list>
<tree><country name="États-Unis"><noRegion><name sortKey="Ghosh, Arun K" sort="Ghosh, Arun K" uniqKey="Ghosh A" first="Arun K." last="Ghosh">Arun K. Ghosh</name>
</noRegion>
<name sortKey="Aubin, Yoann" sort="Aubin, Yoann" uniqKey="Aubin Y" first="Yoann" last="Aubin">Yoann Aubin</name>
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<name sortKey="Chaudhuri, Rima" sort="Chaudhuri, Rima" uniqKey="Chaudhuri R" first="Rima" last="Chaudhuri">Rima Chaudhuri</name>
<name sortKey="Coughlin, Melissa" sort="Coughlin, Melissa" uniqKey="Coughlin M" first="Melissa" last="Coughlin">Melissa Coughlin</name>
<name sortKey="Johnson, Michael E" sort="Johnson, Michael E" uniqKey="Johnson M" first="Michael E." last="Johnson">Michael E. Johnson</name>
<name sortKey="Mesecar, Andrew D" sort="Mesecar, Andrew D" uniqKey="Mesecar A" first="Andrew D." last="Mesecar">Andrew D. Mesecar</name>
<name sortKey="Mulhearn, Debbie C" sort="Mulhearn, Debbie C" uniqKey="Mulhearn D" first="Debbie C." last="Mulhearn">Debbie C. Mulhearn</name>
<name sortKey="Nichols, Daniel B" sort="Nichols, Daniel B" uniqKey="Nichols D" first="Daniel B." last="Nichols">Daniel B. Nichols</name>
<name sortKey="Prabhakar, Bellur S" sort="Prabhakar, Bellur S" uniqKey="Prabhakar B" first="Bellur S." last="Prabhakar">Bellur S. Prabhakar</name>
<name sortKey="Ratia, Kiira" sort="Ratia, Kiira" uniqKey="Ratia K" first="Kiira" last="Ratia">Kiira Ratia</name>
<name sortKey="Sleeman, Katrina" sort="Sleeman, Katrina" uniqKey="Sleeman K" first="Katrina" last="Sleeman">Katrina Sleeman</name>
<name sortKey="Takayama, Jun" sort="Takayama, Jun" uniqKey="Takayama J" first="Jun" last="Takayama">Jun Takayama</name>
</country>
</tree>
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</record>
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