Structure-guided design of potent and permeable inhibitors of MERS coronavirus 3CL protease that utilize a piperidine moiety as a novel design element
Identifieur interne : 000795 ( Main/Exploration ); précédent : 000794; suivant : 000796Structure-guided design of potent and permeable inhibitors of MERS coronavirus 3CL protease that utilize a piperidine moiety as a novel design element
Auteurs : Anushka C. Galasiti Kankanamalage [États-Unis] ; Yunjeong Kim [États-Unis] ; Vishnu C. Damalanka [États-Unis] ; Athri D. Rathnayake [États-Unis] ; Anthony R. Fehr [États-Unis] ; Nurjahan Mehzabeen [États-Unis] ; Kevin P. Battaile [États-Unis] ; Scott Lovell [États-Unis] ; Gerald H. Lushington [États-Unis] ; Stanley Perlman [États-Unis] ; Kyeong-Ok Chang [États-Unis] ; William C. Groutas [États-Unis]Source :
- European Journal of Medicinal Chemistry [ 0223-5234 ] ; 2018.
Descripteurs français
- KwdFr :
- Animaux, Antiviraux (), Antiviraux (pharmacologie), Antiviraux (synthèse chimique), Cellules Vero, Cellules cultivées, Chats, Conception de médicament, Coronavirus du syndrome respiratoire du Moyen-Orient (), Coronavirus du syndrome respiratoire du Moyen-Orient (enzymologie), Cristallographie aux rayons X, Cysteine endopeptidases (métabolisme), Inhibiteurs de la cystéine protéinase (), Inhibiteurs de la cystéine protéinase (pharmacologie), Inhibiteurs de la cystéine protéinase (synthèse chimique), Modèles moléculaires, Mort cellulaire (), Pipéridines (), Pipéridines (pharmacologie), Pipéridines (synthèse chimique), Protéines virales (antagonistes et inhibiteurs), Protéines virales (métabolisme), Relation dose-effet des médicaments, Relation structure-activité, Structure moléculaire.
- MESH :
- antagonistes et inhibiteurs : Protéines virales.
- enzymologie : Coronavirus du syndrome respiratoire du Moyen-Orient.
- métabolisme : Cysteine endopeptidases, Protéines virales.
- pharmacologie : Antiviraux, Inhibiteurs de la cystéine protéinase, Pipéridines.
- synthèse chimique : Antiviraux, Inhibiteurs de la cystéine protéinase, Pipéridines.
- Animaux, Antiviraux, Cellules Vero, Cellules cultivées, Chats, Conception de médicament, Coronavirus du syndrome respiratoire du Moyen-Orient, Cristallographie aux rayons X, Inhibiteurs de la cystéine protéinase, Modèles moléculaires, Mort cellulaire, Pipéridines, Relation dose-effet des médicaments, Relation structure-activité, Structure moléculaire.
English descriptors
- KwdEn :
- Animals, Antiviral Agents (chemical synthesis), Antiviral Agents (chemistry), Antiviral Agents (pharmacology), Cats, Cell Death (drug effects), Cells, Cultured, Chlorocebus aethiops, Crystallography, X-Ray, Cysteine Endopeptidases (metabolism), Cysteine Proteinase Inhibitors (chemical synthesis), Cysteine Proteinase Inhibitors (chemistry), Cysteine Proteinase Inhibitors (pharmacology), Dose-Response Relationship, Drug, Drug Design, Middle East Respiratory Syndrome Coronavirus (drug effects), Middle East Respiratory Syndrome Coronavirus (enzymology), Models, Molecular, Molecular Structure, Piperidines (chemical synthesis), Piperidines (chemistry), Piperidines (pharmacology), Structure-Activity Relationship, Vero Cells, Viral Proteins (antagonists & inhibitors), Viral Proteins (metabolism).
- MESH :
- chemical , antagonists & inhibitors : Viral Proteins.
- chemical , chemical synthesis : Antiviral Agents, Cysteine Proteinase Inhibitors, Piperidines.
- chemical , chemistry : Antiviral Agents, Cysteine Proteinase Inhibitors, Piperidines.
- chemical , metabolism : Cysteine Endopeptidases, Viral Proteins.
- chemical , pharmacology : Antiviral Agents, Cysteine Proteinase Inhibitors, Piperidines.
- drug effects : Cell Death, Middle East Respiratory Syndrome Coronavirus.
- enzymology : Middle East Respiratory Syndrome Coronavirus.
- Animals, Cats, Cells, Cultured, Chlorocebus aethiops, Crystallography, X-Ray, Dose-Response Relationship, Drug, Drug Design, Models, Molecular, Molecular Structure, Structure-Activity Relationship, Vero Cells.
Abstract
There are currently no approved vaccines or small molecule therapeutics available for the prophylaxis or treatment of Middle East Respiratory Syndrome coronavirus (MERS-CoV) infections. MERS-CoV 3CL protease is essential for viral replication; consequently, it is an attractive target that provides a potentially effective means of developing small molecule therapeutics for combatting MERS-CoV. We describe herein the structure-guided design and evaluation of a novel class of inhibitors of MERS-CoV 3CL protease that embody a piperidine moiety as a design element that is well-suited to exploiting favorable subsite binding interactions to attain optimal pharmacological activity and PK properties. The mechanism of action of the compounds and the structural determinants associated with binding were illuminated using X-ray crystallography.
Url:
DOI: 10.1016/j.ejmech.2018.03.004
PubMed: 29544147
PubMed Central: 5891363
Affiliations:
- États-Unis
- Illinois, Iowa, Kansas
- Iowa City, Lawrence (Kansas)
- Université de l'Iowa, Université du Kansas
Links toward previous steps (curation, corpus...)
- to stream Pmc, to step Corpus: 000C57
- to stream Pmc, to step Curation: 000C57
- to stream Pmc, to step Checkpoint: 000459
- to stream PubMed, to step Corpus: 000970
- to stream PubMed, to step Curation: 000970
- to stream PubMed, to step Checkpoint: 000755
- to stream Ncbi, to step Merge: 001D62
- to stream Ncbi, to step Curation: 001D62
- to stream Ncbi, to step Checkpoint: 001D62
- to stream Main, to step Merge: 000798
- to stream Main, to step Curation: 000795
Le document en format XML
<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">Structure-guided design of potent and permeable inhibitors of MERS coronavirus 3CL protease that utilize a piperidine moiety as a novel design element</title><author><name sortKey="Galasiti Kankanamalage, Anushka C" sort="Galasiti Kankanamalage, Anushka C" uniqKey="Galasiti Kankanamalage A" first="Anushka C." last="Galasiti Kankanamalage">Anushka C. Galasiti Kankanamalage</name><affiliation wicri:level="2"><nlm:aff id="aff1">Department of Chemistry, Wichita State University, Wichita, KS 67260, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Chemistry, Wichita State University, Wichita, KS 67260</wicri:regionArea><placeName><region type="state">Kansas</region></placeName></affiliation></author><author><name sortKey="Kim, Yunjeong" sort="Kim, Yunjeong" uniqKey="Kim Y" first="Yunjeong" last="Kim">Yunjeong Kim</name><affiliation wicri:level="2"><nlm:aff id="aff2">Department of Diagnostic Medicine & Pathobiology, College of Veterinary Medicine, Kansas State University, Manhattan, KS 66506, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Diagnostic Medicine & Pathobiology, College of Veterinary Medicine, Kansas State University, Manhattan, KS 66506</wicri:regionArea><placeName><region type="state">Kansas</region></placeName></affiliation></author><author><name sortKey="Damalanka, Vishnu C" sort="Damalanka, Vishnu C" uniqKey="Damalanka V" first="Vishnu C." last="Damalanka">Vishnu C. Damalanka</name><affiliation wicri:level="2"><nlm:aff id="aff1">Department of Chemistry, Wichita State University, Wichita, KS 67260, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Chemistry, Wichita State University, Wichita, KS 67260</wicri:regionArea><placeName><region type="state">Kansas</region></placeName></affiliation></author><author><name sortKey="Rathnayake, Athri D" sort="Rathnayake, Athri D" uniqKey="Rathnayake A" first="Athri D." last="Rathnayake">Athri D. Rathnayake</name><affiliation wicri:level="2"><nlm:aff id="aff1">Department of Chemistry, Wichita State University, Wichita, KS 67260, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Chemistry, Wichita State University, Wichita, KS 67260</wicri:regionArea><placeName><region type="state">Kansas</region></placeName></affiliation></author><author><name sortKey="Fehr, Anthony R" sort="Fehr, Anthony R" uniqKey="Fehr A" first="Anthony R." last="Fehr">Anthony R. Fehr</name><affiliation wicri:level="4"><nlm:aff id="aff6">Department of Microbiology and Immunology, Carver College of Medicine, University of Iowa, Iowa City, IA 52242, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Microbiology and Immunology, Carver College of Medicine, University of Iowa, Iowa City, IA 52242</wicri:regionArea><placeName><region type="state">Iowa</region><settlement type="city">Iowa City</settlement></placeName><orgName type="university">Université de l'Iowa</orgName></affiliation></author><author><name sortKey="Mehzabeen, Nurjahan" sort="Mehzabeen, Nurjahan" uniqKey="Mehzabeen N" first="Nurjahan" last="Mehzabeen">Nurjahan Mehzabeen</name><affiliation wicri:level="4"><nlm:aff id="aff3">Protein Structure Laboratory, The University of Kansas, Lawrence, KS 66047, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Protein Structure Laboratory, The University of Kansas, Lawrence, KS 66047</wicri:regionArea><placeName><region type="state">Kansas</region><settlement type="city">Lawrence (Kansas)</settlement></placeName><orgName type="university">Université du Kansas</orgName></affiliation></author><author><name sortKey="Battaile, Kevin P" sort="Battaile, Kevin P" uniqKey="Battaile K" first="Kevin P." last="Battaile">Kevin P. Battaile</name><affiliation wicri:level="2"><nlm:aff id="aff4">IMCA-CAT, Hauptman-Woodward Medical Research Institute, APS Argonne National Laboratory, Argonne, IL 60439, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>IMCA-CAT, Hauptman-Woodward Medical Research Institute, APS Argonne National Laboratory, Argonne, IL 60439</wicri:regionArea><placeName><region type="state">Illinois</region></placeName></affiliation></author><author><name sortKey="Lovell, Scott" sort="Lovell, Scott" uniqKey="Lovell S" first="Scott" last="Lovell">Scott Lovell</name><affiliation wicri:level="4"><nlm:aff id="aff3">Protein Structure Laboratory, The University of Kansas, Lawrence, KS 66047, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Protein Structure Laboratory, The University of Kansas, Lawrence, KS 66047</wicri:regionArea><placeName><region type="state">Kansas</region><settlement type="city">Lawrence (Kansas)</settlement></placeName><orgName type="university">Université du Kansas</orgName></affiliation></author><author><name sortKey="Lushington, Gerald H" sort="Lushington, Gerald H" uniqKey="Lushington G" first="Gerald H." last="Lushington">Gerald H. Lushington</name><affiliation wicri:level="2"><nlm:aff id="aff5">LiS Consulting, Lawrence, KS 66046, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>LiS Consulting, Lawrence, KS 66046</wicri:regionArea><placeName><region type="state">Kansas</region></placeName></affiliation></author><author><name sortKey="Perlman, Stanley" sort="Perlman, Stanley" uniqKey="Perlman S" first="Stanley" last="Perlman">Stanley Perlman</name><affiliation wicri:level="4"><nlm:aff id="aff6">Department of Microbiology and Immunology, Carver College of Medicine, University of Iowa, Iowa City, IA 52242, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Microbiology and Immunology, Carver College of Medicine, University of Iowa, Iowa City, IA 52242</wicri:regionArea><placeName><region type="state">Iowa</region><settlement type="city">Iowa City</settlement></placeName><orgName type="university">Université de l'Iowa</orgName></affiliation></author><author><name sortKey="Chang, Kyeong Ok" sort="Chang, Kyeong Ok" uniqKey="Chang K" first="Kyeong-Ok" last="Chang">Kyeong-Ok Chang</name><affiliation wicri:level="2"><nlm:aff id="aff2">Department of Diagnostic Medicine & Pathobiology, College of Veterinary Medicine, Kansas State University, Manhattan, KS 66506, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Diagnostic Medicine & Pathobiology, College of Veterinary Medicine, Kansas State University, Manhattan, KS 66506</wicri:regionArea><placeName><region type="state">Kansas</region></placeName></affiliation></author><author><name sortKey="Groutas, William C" sort="Groutas, William C" uniqKey="Groutas W" first="William C." last="Groutas">William C. Groutas</name><affiliation wicri:level="2"><nlm:aff id="aff1">Department of Chemistry, Wichita State University, Wichita, KS 67260, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Chemistry, Wichita State University, Wichita, KS 67260</wicri:regionArea><placeName><region type="state">Kansas</region></placeName></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PMC</idno><idno type="pmid">29544147</idno><idno type="pmc">5891363</idno><idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5891363</idno><idno type="RBID">PMC:5891363</idno><idno type="doi">10.1016/j.ejmech.2018.03.004</idno><date when="2018">2018</date><idno type="wicri:Area/Pmc/Corpus">000C57</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Corpus" wicri:corpus="PMC">000C57</idno><idno type="wicri:Area/Pmc/Curation">000C57</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Curation">000C57</idno><idno type="wicri:Area/Pmc/Checkpoint">000459</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Checkpoint">000459</idno><idno type="wicri:source">PubMed</idno><idno type="RBID">pubmed:29544147</idno><idno type="wicri:Area/PubMed/Corpus">000970</idno><idno type="wicri:explorRef" wicri:stream="PubMed" wicri:step="Corpus" wicri:corpus="PubMed">000970</idno><idno type="wicri:Area/PubMed/Curation">000970</idno><idno type="wicri:explorRef" wicri:stream="PubMed" wicri:step="Curation">000970</idno><idno type="wicri:Area/PubMed/Checkpoint">000755</idno><idno type="wicri:explorRef" wicri:stream="Checkpoint" wicri:step="PubMed">000755</idno><idno type="wicri:Area/Ncbi/Merge">001D62</idno><idno type="wicri:Area/Ncbi/Curation">001D62</idno><idno type="wicri:Area/Ncbi/Checkpoint">001D62</idno><idno type="wicri:doubleKey">0223-5234:2018:Galasiti Kankanamalage A:structure:guided:design</idno><idno type="wicri:Area/Main/Merge">000798</idno><idno type="wicri:Area/Main/Curation">000795</idno><idno type="wicri:Area/Main/Exploration">000795</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">Structure-guided design of potent and permeable inhibitors of MERS coronavirus 3CL protease that utilize a piperidine moiety as a novel design element</title><author><name sortKey="Galasiti Kankanamalage, Anushka C" sort="Galasiti Kankanamalage, Anushka C" uniqKey="Galasiti Kankanamalage A" first="Anushka C." last="Galasiti Kankanamalage">Anushka C. Galasiti Kankanamalage</name><affiliation wicri:level="2"><nlm:aff id="aff1">Department of Chemistry, Wichita State University, Wichita, KS 67260, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Chemistry, Wichita State University, Wichita, KS 67260</wicri:regionArea><placeName><region type="state">Kansas</region></placeName></affiliation></author><author><name sortKey="Kim, Yunjeong" sort="Kim, Yunjeong" uniqKey="Kim Y" first="Yunjeong" last="Kim">Yunjeong Kim</name><affiliation wicri:level="2"><nlm:aff id="aff2">Department of Diagnostic Medicine & Pathobiology, College of Veterinary Medicine, Kansas State University, Manhattan, KS 66506, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Diagnostic Medicine & Pathobiology, College of Veterinary Medicine, Kansas State University, Manhattan, KS 66506</wicri:regionArea><placeName><region type="state">Kansas</region></placeName></affiliation></author><author><name sortKey="Damalanka, Vishnu C" sort="Damalanka, Vishnu C" uniqKey="Damalanka V" first="Vishnu C." last="Damalanka">Vishnu C. Damalanka</name><affiliation wicri:level="2"><nlm:aff id="aff1">Department of Chemistry, Wichita State University, Wichita, KS 67260, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Chemistry, Wichita State University, Wichita, KS 67260</wicri:regionArea><placeName><region type="state">Kansas</region></placeName></affiliation></author><author><name sortKey="Rathnayake, Athri D" sort="Rathnayake, Athri D" uniqKey="Rathnayake A" first="Athri D." last="Rathnayake">Athri D. Rathnayake</name><affiliation wicri:level="2"><nlm:aff id="aff1">Department of Chemistry, Wichita State University, Wichita, KS 67260, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Chemistry, Wichita State University, Wichita, KS 67260</wicri:regionArea><placeName><region type="state">Kansas</region></placeName></affiliation></author><author><name sortKey="Fehr, Anthony R" sort="Fehr, Anthony R" uniqKey="Fehr A" first="Anthony R." last="Fehr">Anthony R. Fehr</name><affiliation wicri:level="4"><nlm:aff id="aff6">Department of Microbiology and Immunology, Carver College of Medicine, University of Iowa, Iowa City, IA 52242, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Microbiology and Immunology, Carver College of Medicine, University of Iowa, Iowa City, IA 52242</wicri:regionArea><placeName><region type="state">Iowa</region><settlement type="city">Iowa City</settlement></placeName><orgName type="university">Université de l'Iowa</orgName></affiliation></author><author><name sortKey="Mehzabeen, Nurjahan" sort="Mehzabeen, Nurjahan" uniqKey="Mehzabeen N" first="Nurjahan" last="Mehzabeen">Nurjahan Mehzabeen</name><affiliation wicri:level="4"><nlm:aff id="aff3">Protein Structure Laboratory, The University of Kansas, Lawrence, KS 66047, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Protein Structure Laboratory, The University of Kansas, Lawrence, KS 66047</wicri:regionArea><placeName><region type="state">Kansas</region><settlement type="city">Lawrence (Kansas)</settlement></placeName><orgName type="university">Université du Kansas</orgName></affiliation></author><author><name sortKey="Battaile, Kevin P" sort="Battaile, Kevin P" uniqKey="Battaile K" first="Kevin P." last="Battaile">Kevin P. Battaile</name><affiliation wicri:level="2"><nlm:aff id="aff4">IMCA-CAT, Hauptman-Woodward Medical Research Institute, APS Argonne National Laboratory, Argonne, IL 60439, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>IMCA-CAT, Hauptman-Woodward Medical Research Institute, APS Argonne National Laboratory, Argonne, IL 60439</wicri:regionArea><placeName><region type="state">Illinois</region></placeName></affiliation></author><author><name sortKey="Lovell, Scott" sort="Lovell, Scott" uniqKey="Lovell S" first="Scott" last="Lovell">Scott Lovell</name><affiliation wicri:level="4"><nlm:aff id="aff3">Protein Structure Laboratory, The University of Kansas, Lawrence, KS 66047, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Protein Structure Laboratory, The University of Kansas, Lawrence, KS 66047</wicri:regionArea><placeName><region type="state">Kansas</region><settlement type="city">Lawrence (Kansas)</settlement></placeName><orgName type="university">Université du Kansas</orgName></affiliation></author><author><name sortKey="Lushington, Gerald H" sort="Lushington, Gerald H" uniqKey="Lushington G" first="Gerald H." last="Lushington">Gerald H. Lushington</name><affiliation wicri:level="2"><nlm:aff id="aff5">LiS Consulting, Lawrence, KS 66046, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>LiS Consulting, Lawrence, KS 66046</wicri:regionArea><placeName><region type="state">Kansas</region></placeName></affiliation></author><author><name sortKey="Perlman, Stanley" sort="Perlman, Stanley" uniqKey="Perlman S" first="Stanley" last="Perlman">Stanley Perlman</name><affiliation wicri:level="4"><nlm:aff id="aff6">Department of Microbiology and Immunology, Carver College of Medicine, University of Iowa, Iowa City, IA 52242, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Microbiology and Immunology, Carver College of Medicine, University of Iowa, Iowa City, IA 52242</wicri:regionArea><placeName><region type="state">Iowa</region><settlement type="city">Iowa City</settlement></placeName><orgName type="university">Université de l'Iowa</orgName></affiliation></author><author><name sortKey="Chang, Kyeong Ok" sort="Chang, Kyeong Ok" uniqKey="Chang K" first="Kyeong-Ok" last="Chang">Kyeong-Ok Chang</name><affiliation wicri:level="2"><nlm:aff id="aff2">Department of Diagnostic Medicine & Pathobiology, College of Veterinary Medicine, Kansas State University, Manhattan, KS 66506, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Diagnostic Medicine & Pathobiology, College of Veterinary Medicine, Kansas State University, Manhattan, KS 66506</wicri:regionArea><placeName><region type="state">Kansas</region></placeName></affiliation></author><author><name sortKey="Groutas, William C" sort="Groutas, William C" uniqKey="Groutas W" first="William C." last="Groutas">William C. Groutas</name><affiliation wicri:level="2"><nlm:aff id="aff1">Department of Chemistry, Wichita State University, Wichita, KS 67260, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Chemistry, Wichita State University, Wichita, KS 67260</wicri:regionArea><placeName><region type="state">Kansas</region></placeName></affiliation></author></analytic><series><title level="j">European Journal of Medicinal Chemistry</title><idno type="ISSN">0223-5234</idno><idno type="eISSN">1768-3254</idno><imprint><date when="2018">2018</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Animals</term><term>Antiviral Agents (chemical synthesis)</term><term>Antiviral Agents (chemistry)</term><term>Antiviral Agents (pharmacology)</term><term>Cats</term><term>Cell Death (drug effects)</term><term>Cells, Cultured</term><term>Chlorocebus aethiops</term><term>Crystallography, X-Ray</term><term>Cysteine Endopeptidases (metabolism)</term><term>Cysteine Proteinase Inhibitors (chemical synthesis)</term><term>Cysteine Proteinase Inhibitors (chemistry)</term><term>Cysteine Proteinase Inhibitors (pharmacology)</term><term>Dose-Response Relationship, Drug</term><term>Drug Design</term><term>Middle East Respiratory Syndrome Coronavirus (drug effects)</term><term>Middle East Respiratory Syndrome Coronavirus (enzymology)</term><term>Models, Molecular</term><term>Molecular Structure</term><term>Piperidines (chemical synthesis)</term><term>Piperidines (chemistry)</term><term>Piperidines (pharmacology)</term><term>Structure-Activity Relationship</term><term>Vero Cells</term><term>Viral Proteins (antagonists & inhibitors)</term><term>Viral Proteins (metabolism)</term></keywords><keywords scheme="KwdFr" xml:lang="fr"><term>Animaux</term><term>Antiviraux ()</term><term>Antiviraux (pharmacologie)</term><term>Antiviraux (synthèse chimique)</term><term>Cellules Vero</term><term>Cellules cultivées</term><term>Chats</term><term>Conception de médicament</term><term>Coronavirus du syndrome respiratoire du Moyen-Orient ()</term><term>Coronavirus du syndrome respiratoire du Moyen-Orient (enzymologie)</term><term>Cristallographie aux rayons X</term><term>Cysteine endopeptidases (métabolisme)</term><term>Inhibiteurs de la cystéine protéinase ()</term><term>Inhibiteurs de la cystéine protéinase (pharmacologie)</term><term>Inhibiteurs de la cystéine protéinase (synthèse chimique)</term><term>Modèles moléculaires</term><term>Mort cellulaire ()</term><term>Pipéridines ()</term><term>Pipéridines (pharmacologie)</term><term>Pipéridines (synthèse chimique)</term><term>Protéines virales (antagonistes et inhibiteurs)</term><term>Protéines virales (métabolisme)</term><term>Relation dose-effet des médicaments</term><term>Relation structure-activité</term><term>Structure moléculaire</term></keywords><keywords scheme="MESH" type="chemical" qualifier="antagonists & inhibitors" xml:lang="en"><term>Viral Proteins</term></keywords><keywords scheme="MESH" type="chemical" qualifier="chemical synthesis" xml:lang="en"><term>Antiviral Agents</term><term>Cysteine Proteinase Inhibitors</term><term>Piperidines</term></keywords><keywords scheme="MESH" type="chemical" qualifier="chemistry" xml:lang="en"><term>Antiviral Agents</term><term>Cysteine Proteinase Inhibitors</term><term>Piperidines</term></keywords><keywords scheme="MESH" type="chemical" qualifier="metabolism" xml:lang="en"><term>Cysteine Endopeptidases</term><term>Viral Proteins</term></keywords><keywords scheme="MESH" type="chemical" qualifier="pharmacology" xml:lang="en"><term>Antiviral Agents</term><term>Cysteine Proteinase Inhibitors</term><term>Piperidines</term></keywords><keywords scheme="MESH" qualifier="antagonistes et inhibiteurs" xml:lang="fr"><term>Protéines virales</term></keywords><keywords scheme="MESH" qualifier="drug effects" xml:lang="en"><term>Cell Death</term><term>Middle East Respiratory Syndrome Coronavirus</term></keywords><keywords scheme="MESH" qualifier="enzymologie" xml:lang="fr"><term>Coronavirus du syndrome respiratoire du Moyen-Orient</term></keywords><keywords scheme="MESH" qualifier="enzymology" xml:lang="en"><term>Middle East Respiratory Syndrome Coronavirus</term></keywords><keywords scheme="MESH" qualifier="métabolisme" xml:lang="fr"><term>Cysteine endopeptidases</term><term>Protéines virales</term></keywords><keywords scheme="MESH" qualifier="pharmacologie" xml:lang="fr"><term>Antiviraux</term><term>Inhibiteurs de la cystéine protéinase</term><term>Pipéridines</term></keywords><keywords scheme="MESH" qualifier="synthèse chimique" xml:lang="fr"><term>Antiviraux</term><term>Inhibiteurs de la cystéine protéinase</term><term>Pipéridines</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Animals</term><term>Cats</term><term>Cells, Cultured</term><term>Chlorocebus aethiops</term><term>Crystallography, X-Ray</term><term>Dose-Response Relationship, Drug</term><term>Drug Design</term><term>Models, Molecular</term><term>Molecular Structure</term><term>Structure-Activity Relationship</term><term>Vero Cells</term></keywords><keywords scheme="MESH" xml:lang="fr"><term>Animaux</term><term>Antiviraux</term><term>Cellules Vero</term><term>Cellules cultivées</term><term>Chats</term><term>Conception de médicament</term><term>Coronavirus du syndrome respiratoire du Moyen-Orient</term><term>Cristallographie aux rayons X</term><term>Inhibiteurs de la cystéine protéinase</term><term>Modèles moléculaires</term><term>Mort cellulaire</term><term>Pipéridines</term><term>Relation dose-effet des médicaments</term><term>Relation structure-activité</term><term>Structure moléculaire</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><p>There are currently no approved vaccines or small molecule therapeutics available for the prophylaxis or treatment of Middle East Respiratory Syndrome coronavirus (MERS-CoV) infections. MERS-CoV 3CL protease is essential for viral replication; consequently, it is an attractive target that provides a potentially effective means of developing small molecule therapeutics for combatting MERS-CoV. We describe herein the structure-guided design and evaluation of a novel class of inhibitors of MERS-CoV 3CL protease that embody a piperidine moiety as a design element that is well-suited to exploiting favorable subsite binding interactions to attain optimal pharmacological activity and PK properties. The mechanism of action of the compounds and the structural determinants associated with binding were illuminated using X-ray crystallography.</p></div></front><back><div1 type="bibliography"><listBibl><biblStruct><analytic><author><name sortKey="Masters, P S" uniqKey="Masters P">P.S. Masters</name></author><author><name sortKey="Perlman, S" uniqKey="Perlman S">S. Perlman</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Coleman, C M" uniqKey="Coleman C">C.M. Coleman</name></author><author><name sortKey="Frieman, M B" uniqKey="Frieman M">M.B. Frieman</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="De Wit, E" uniqKey="De Wit E">E. De Wit</name></author><author><name sortKey="Van Doremalen, N" uniqKey="Van Doremalen N">N. van Doremalen</name></author><author><name sortKey="Falzarano, D" uniqKey="Falzarano D">D. Falzarano</name></author><author><name sortKey="Munster, V J" uniqKey="Munster V">V.J. Munster</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Greenberg, S B" uniqKey="Greenberg S">S.B. Greenberg</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Vijay, R" uniqKey="Vijay R">R. Vijay</name></author><author><name sortKey="Perlman, S" uniqKey="Perlman S">S. Perlman</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Van Den Brand, J M A" uniqKey="Van Den Brand J">J.M.A. Van den Brand</name></author><author><name sortKey="Smits, S L" uniqKey="Smits S">S.L. Smits</name></author><author><name sortKey="Haagmans, B L" uniqKey="Haagmans B">B.L. Haagmans</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Chan, J F W" uniqKey="Chan J">J.F.W. Chan</name></author><author><name sortKey="Lau, S K P" uniqKey="Lau S">S.K.P. Lau</name></author><author><name sortKey="To, K K W" uniqKey="To K">K.K.W. To</name></author><author><name sortKey="Cheng, V C C" uniqKey="Cheng V">V.C.C. Cheng</name></author><author><name sortKey="Woo, P C Y" uniqKey="Woo P">P.C.Y. Woo</name></author><author><name sortKey="Yuen, K Y" uniqKey="Yuen K">K.-Y. Yuen</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Hui, D S" uniqKey="Hui D">D.S. Hui</name></author><author><name sortKey="Peiris, M" uniqKey="Peiris M">M. Peiris</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Zumla, A" uniqKey="Zumla A">A. Zumla</name></author><author><name sortKey="Chan, J F" uniqKey="Chan J">J.F. Chan</name></author><author><name sortKey="Azhar, E" uniqKey="Azhar E">E. Azhar</name></author><author><name sortKey="Hui, D S" uniqKey="Hui D">D.S. Hui</name></author><author><name sortKey="Yuen, K Y" uniqKey="Yuen K">K.-Y. Yuen</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Adedeji, A O" uniqKey="Adedeji A">A.O. Adedeji</name></author><author><name sortKey="Sarafianos, S G" uniqKey="Sarafianos S">S.G. Sarafianos</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Modjarrad, K" uniqKey="Modjarrad K">K. Modjarrad</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Qian, Z" uniqKey="Qian Z">Z. Qian</name></author><author><name sortKey="Dominguez, S R" uniqKey="Dominguez S">S.R. Dominguez</name></author><author><name sortKey="Holmes, K V" uniqKey="Holmes K">K.V. Holmes</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Shirato, K" uniqKey="Shirato K">K. Shirato</name></author><author><name sortKey="Kawase, M" uniqKey="Kawase M">M. Kawase</name></author><author><name sortKey="Matsuyama, S" uniqKey="Matsuyama S">S. Matsuyama</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Miller, J K" uniqKey="Miller J">J.K. Miller</name></author><author><name sortKey="Whittaker, G R" uniqKey="Whittaker G">G.R. Whittaker</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Pillaiyar, T" uniqKey="Pillaiyar T">T. Pillaiyar</name></author><author><name sortKey="Manickam, M" uniqKey="Manickam M">M. Manickam</name></author><author><name sortKey="Namasivayam, V" uniqKey="Namasivayam V">V. Namasivayam</name></author><author><name sortKey="Hayashi, Y" uniqKey="Hayashi Y">Y. Hayashi</name></author><author><name sortKey="Jung, S H" uniqKey="Jung S">S.-H. Jung</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Baez Santos, Y M" uniqKey="Baez Santos Y">Y.M. Baez-Santos</name></author><author><name sortKey="St John, S E" uniqKey="St John S">S.E. St. John</name></author><author><name sortKey="Mesecar, A D" uniqKey="Mesecar A">A.D. Mesecar</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Kumar, V" uniqKey="Kumar V">V. Kumar</name></author><author><name sortKey="Tan, K P" uniqKey="Tan K">K.-P. Tan</name></author><author><name sortKey="Wang, Y M" uniqKey="Wang Y">Y.-M. Wang</name></author><author><name sortKey="Lin, S W" uniqKey="Lin S">S.-W. Lin</name></author><author><name sortKey="Liang, P H" uniqKey="Liang P">P.-H. Liang</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Needle, D" uniqKey="Needle D">D. Needle</name></author><author><name sortKey="Lountos, G T" uniqKey="Lountos G">G.T. Lountos</name></author><author><name sortKey="Waugh, D S" uniqKey="Waugh D">D.S. Waugh</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Hilgenfeld, R" uniqKey="Hilgenfeld R">R. Hilgenfeld</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Wu, A" uniqKey="Wu A">A. Wu</name></author><author><name sortKey="Wang, Y" uniqKey="Wang Y">Y. Wang</name></author><author><name sortKey="Zeng, C" uniqKey="Zeng C">C. Zeng</name></author><author><name sortKey="Huang, X" uniqKey="Huang X">X. Huang</name></author><author><name sortKey="Xu, S" uniqKey="Xu S">S. Xu</name></author><author><name sortKey="Su, C" uniqKey="Su C">C. Su</name></author><author><name sortKey="Wang, M" uniqKey="Wang M">M. Wang</name></author><author><name sortKey="Chen, Y" uniqKey="Chen Y">Y. Chen</name></author><author><name sortKey="Guo, D" uniqKey="Guo D">D. Guo</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Lee, H" uniqKey="Lee H">H. Lee</name></author><author><name sortKey="Lei, H" uniqKey="Lei H">H. Lei</name></author><author><name sortKey="Santarsiero, B D" uniqKey="Santarsiero B">B.D. Santarsiero</name></author><author><name sortKey="Gatuz, J L" uniqKey="Gatuz J">J.L. Gatuz</name></author><author><name sortKey="Cao, S" uniqKey="Cao S">S. Cao</name></author><author><name sortKey="Rice, A J" uniqKey="Rice A">A.J. Rice</name></author><author><name sortKey="Patel, K" uniqKey="Patel K">K. Patel</name></author><author><name sortKey="Szypulinski, M" uniqKey="Szypulinski M">M. Szypulinski</name></author><author><name sortKey="Ojeda, I" uniqKey="Ojeda I">I. Ojeda</name></author><author><name sortKey="Ghosh, A K" uniqKey="Ghosh A">A.K. Ghosh</name></author><author><name sortKey="Johnson, M E" uniqKey="Johnson M">M.E. Johnson</name></author></analytic></biblStruct><biblStruct></biblStruct><biblStruct><analytic><author><name sortKey="Wang, F" uniqKey="Wang F">F. Wang</name></author><author><name sortKey="Chen, C" uniqKey="Chen C">C. Chen</name></author><author><name sortKey="Tan, W" uniqKey="Tan W">W. Tan</name></author><author><name sortKey="Yang, K" uniqKey="Yang K">K. Yang</name></author><author><name sortKey="Yang, H" uniqKey="Yang H">H. Yang</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Kim, Y" uniqKey="Kim Y">Y. Kim</name></author><author><name sortKey="Liu, H" uniqKey="Liu H">H. Liu</name></author><author><name sortKey="Galasiti Kankanamalage, A C" uniqKey="Galasiti Kankanamalage A">A.C. Galasiti Kankanamalage</name></author><author><name sortKey="Weerasekara, S" uniqKey="Weerasekara S">S. Weerasekara</name></author><author><name sortKey="Hua, D H" uniqKey="Hua D">D.H. Hua</name></author><author><name sortKey="Groutas, W C" uniqKey="Groutas W">W.C. Groutas</name></author><author><name sortKey="Chang, K O" uniqKey="Chang K">K.O. Chang</name></author><author><name sortKey="Pedersen, N C" uniqKey="Pedersen N">N.C. Pedersen</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Pedersen, N C" uniqKey="Pedersen N">N.C. Pedersen</name></author><author><name sortKey="Kim, Y" uniqKey="Kim Y">Y. Kim</name></author><author><name sortKey="Liu, H" uniqKey="Liu H">H. Liu</name></author><author><name sortKey="Galasiti Kankanamalage, A C" uniqKey="Galasiti Kankanamalage A">A.C. Galasiti Kankanamalage</name></author><author><name sortKey="Eckstrand, C" uniqKey="Eckstrand C">C. Eckstrand</name></author><author><name sortKey="Groutas, W C" uniqKey="Groutas W">W.C. Groutas</name></author><author><name sortKey="Bannasch, M" uniqKey="Bannasch M">M. Bannasch</name></author><author><name sortKey="Meadows, J M" uniqKey="Meadows J">J.M. Meadows</name></author><author><name sortKey="Chang, K O" uniqKey="Chang K">K.O. Chang</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Webster, S E" uniqKey="Webster S">S.E. Webster</name></author><author><name sortKey="Okano, K" uniqKey="Okano K">K. Okano</name></author><author><name sortKey="Little, T L" uniqKey="Little T">T.L. Little</name></author><author><name sortKey="Reich, S H" uniqKey="Reich S">S.H. Reich</name></author><author><name sortKey="Xin, Y" uniqKey="Xin Y">Y. Xin</name></author><author><name sortKey="Fuhrman, S A" uniqKey="Fuhrman S">S.A. Fuhrman</name></author><author><name sortKey="Matthews, D A" uniqKey="Matthews D">D.A. Matthews</name></author><author><name sortKey="Love, R A" uniqKey="Love R">R.A. Love</name></author><author><name sortKey="Hendrickson, T F" uniqKey="Hendrickson T">T.F. Hendrickson</name></author><author><name sortKey="Patick, A K" uniqKey="Patick A">A.K. Patick</name></author><author><name sortKey="Meador, J W" uniqKey="Meador J">J.W. Meador</name></author><author><name sortKey="Ferre, R A" uniqKey="Ferre R">R.A. Ferre</name></author><author><name sortKey="Brown, E L" uniqKey="Brown E">E.L. Brown</name></author><author><name sortKey="Ford, C E" uniqKey="Ford C">C.E. Ford</name></author><author><name sortKey="Binford, S L" uniqKey="Binford S">S.L. Binford</name></author><author><name sortKey="Worland, S T" uniqKey="Worland S">S.T. Worland</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Galasiti Kankanamalage, A C" uniqKey="Galasiti Kankanamalage A">A.C. Galasiti Kankanamalage</name></author><author><name sortKey="Kim, Y" uniqKey="Kim Y">Y. Kim</name></author><author><name sortKey="Weerawarna, P W" uniqKey="Weerawarna P">P.W. Weerawarna</name></author><author><name sortKey="Uy, R A Z" uniqKey="Uy R">R.A.Z. Uy</name></author><author><name sortKey="Damalanka, V C" uniqKey="Damalanka V">V.C. Damalanka</name></author><author><name sortKey="Mndadapu, S R" uniqKey="Mndadapu S">S.R. Mndadapu</name></author><author><name sortKey="Alliston, K R" uniqKey="Alliston K">K.R. Alliston</name></author><author><name sortKey="Mehzabeen, N" uniqKey="Mehzabeen N">N. Mehzabeen</name></author><author><name sortKey="Battaille, K P" uniqKey="Battaille K">K.P. Battaille</name></author><author><name sortKey="Lovell, S" uniqKey="Lovell S">S. Lovell</name></author><author><name sortKey="Chang, K O" uniqKey="Chang K">K.-O. Chang</name></author><author><name sortKey="Groutas, W C" uniqKey="Groutas W">W.C. Groutas</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Mandadapu, S R" uniqKey="Mandadapu S">S.R. Mandadapu</name></author><author><name sortKey="Gunnam, M R" uniqKey="Gunnam M">M.R. Gunnam</name></author><author><name sortKey="Tiew, K C" uniqKey="Tiew K">K.-C. Tiew</name></author><author><name sortKey="Uy, R A Z" uniqKey="Uy R">R.A.Z. Uy</name></author><author><name sortKey="Prior, A M" uniqKey="Prior A">A.M. Prior</name></author><author><name sortKey="Alliston, K R" uniqKey="Alliston K">K.R. Alliston</name></author><author><name sortKey="Hua, D H" uniqKey="Hua D">D.H. Hua</name></author><author><name sortKey="Kim, Y" uniqKey="Kim Y">Y. Kim</name></author><author><name sortKey="Chang, K O" uniqKey="Chang K">K.-O. Chang</name></author><author><name sortKey="Groutas, W C" uniqKey="Groutas W">W.C. Groutas</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Kim, Y" uniqKey="Kim Y">Y. Kim</name></author><author><name sortKey="Lovell, S" uniqKey="Lovell S">S. Lovell</name></author><author><name sortKey="Tiew, K C" uniqKey="Tiew K">K.C. Tiew</name></author><author><name sortKey="Mandadapu, S R" uniqKey="Mandadapu S">S.R. Mandadapu</name></author><author><name sortKey="Alliston, K R" uniqKey="Alliston K">K.R. Alliston</name></author><author><name sortKey="Battaille, K P" uniqKey="Battaille K">K.P. Battaille</name></author><author><name sortKey="Groutas, W C" uniqKey="Groutas W">W.C. Groutas</name></author><author><name sortKey="Chang, K O" uniqKey="Chang K">K.-O. Chang</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="De Wilde, A H" uniqKey="De Wilde A">A.H. de Wilde</name></author><author><name sortKey="Falzarano, D" uniqKey="Falzarano D">D. Falzarano</name></author><author><name sortKey="Zevenhoven Dobbe, J C" uniqKey="Zevenhoven Dobbe J">J.C. Zevenhoven-Dobbe</name></author><author><name sortKey="Beugeling, C" uniqKey="Beugeling C">C. Beugeling</name></author><author><name sortKey="Fett, C" uniqKey="Fett C">C. Fett</name></author><author><name sortKey="Martellaro, C" uniqKey="Martellaro C">C. Martellaro</name></author><author><name sortKey="Posthuma, C C" uniqKey="Posthuma C">C.C. Posthuma</name></author><author><name sortKey="Feldmann, H" uniqKey="Feldmann H">H. Feldmann</name></author><author><name sortKey="Perlman, S" uniqKey="Perlman S">S. Perlman</name></author><author><name sortKey="Snijder, E J" uniqKey="Snijder E">E.J. Snijder</name></author></analytic></biblStruct><biblStruct></biblStruct><biblStruct><analytic><author><name sortKey="Kabsch, W" uniqKey="Kabsch W">W. Kabsch</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Kabsch, W" uniqKey="Kabsch W">W. Kabsch</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Vonrhein, C" uniqKey="Vonrhein C">C. Vonrhein</name></author><author><name sortKey="Flensburg, C" uniqKey="Flensburg C">C. Flensburg</name></author><author><name sortKey="Keller, P" uniqKey="Keller P">P. Keller</name></author><author><name sortKey="Sharff, A" uniqKey="Sharff A">A. Sharff</name></author><author><name sortKey="Smart, O" uniqKey="Smart O">O. Smart</name></author><author><name sortKey="Paciorek, W" uniqKey="Paciorek W">W. Paciorek</name></author><author><name sortKey="Womack, T" uniqKey="Womack T">T. Womack</name></author><author><name sortKey="Bricogne, G" uniqKey="Bricogne G">G. Bricogne</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Evans, P R" uniqKey="Evans P">P.R. Evans</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Mccoy, A J" uniqKey="Mccoy A">A.J. McCoy</name></author><author><name sortKey="Grosse Kunstleve, R W" uniqKey="Grosse Kunstleve R">R.W. Grosse-Kunstleve</name></author><author><name sortKey="Adams, P D" uniqKey="Adams P">P.D. Adams</name></author><author><name sortKey="Winn, M" uniqKey="Winn M">M. Winn</name></author><author><name sortKey="Storoni, L C" uniqKey="Storoni L">L.C. Storoni</name></author><author><name sortKey="Read, R J" uniqKey="Read R">R.J. Read</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Johnston, T S" uniqKey="Johnston T">T.S. Johnston</name></author><author><name sortKey="St John, S E" uniqKey="St John S">S.E. St. John</name></author><author><name sortKey="Osswald, H L" uniqKey="Osswald H">H.L. Osswald</name></author><author><name sortKey="Nyalapatla, P R" uniqKey="Nyalapatla P">P.R. Nyalapatla</name></author><author><name sortKey="Paul, L N" uniqKey="Paul L">L.N. Paul</name></author><author><name sortKey="Ghosh, A K" uniqKey="Ghosh A">A.K. Ghosh</name></author><author><name sortKey="Denison, M R" uniqKey="Denison M">M.R. Denison</name></author><author><name sortKey="Mesecar, A D" uniqKey="Mesecar A">A.D. Mesecar</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Adams, P D" uniqKey="Adams P">P.D. Adams</name></author><author><name sortKey="Afonine, P V" uniqKey="Afonine P">P.V. Afonine</name></author><author><name sortKey="Bunkoczi, G" uniqKey="Bunkoczi G">G. Bunkoczi</name></author><author><name sortKey="Chen, V B" uniqKey="Chen V">V.B. Chen</name></author><author><name sortKey="David, I W" uniqKey="David I">I.W. David</name></author><author><name sortKey="Echols, N" uniqKey="Echols N">N. Echols</name></author><author><name sortKey="Headd, J J" uniqKey="Headd J">J.J. Headd</name></author><author><name sortKey="Hung, L W" uniqKey="Hung L">L.W. Hung</name></author><author><name sortKey="Kapral, G J" uniqKey="Kapral G">G.J. Kapral</name></author><author><name sortKey="Grosse Kunstleve, R W" uniqKey="Grosse Kunstleve R">R.W. Grosse-Kunstleve</name></author><author><name sortKey="Mccoy, A J" uniqKey="Mccoy A">A.J. McCoy</name></author><author><name sortKey="Moriarty, N W" uniqKey="Moriarty N">N.W. Moriarty</name></author><author><name sortKey="Oeffner, R" uniqKey="Oeffner R">R. Oeffner</name></author><author><name sortKey="Read, R J" uniqKey="Read R">R.J. Read</name></author><author><name sortKey="Richardson, D C" uniqKey="Richardson D">D.C. Richardson</name></author><author><name sortKey="Richardson, J S" uniqKey="Richardson J">J.S. Richardson</name></author><author><name sortKey="Terwilliger, T C" uniqKey="Terwilliger T">T.C. Terwilliger</name></author><author><name sortKey="Zwart, P H" uniqKey="Zwart P">P.H. Zwart</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Emsley, P" uniqKey="Emsley P">P. Emsley</name></author><author><name sortKey="Lohkamp, B" uniqKey="Lohkamp B">B. Lohkamp</name></author><author><name sortKey="Scott, W G" uniqKey="Scott W">W.G. Scott</name></author><author><name sortKey="Cowtan, K" uniqKey="Cowtan K">K. Cowtan</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Chen, V B" uniqKey="Chen V">V.B. Chen</name></author><author><name sortKey="Arendall, W B" uniqKey="Arendall W">W.B. Arendall</name></author><author><name sortKey="Headd, J J" uniqKey="Headd J">J.J. Headd</name></author><author><name sortKey="Keedy, D A" uniqKey="Keedy D">D.A. Keedy</name></author><author><name sortKey="Immormino, R M" uniqKey="Immormino R">R.M. Immormino</name></author><author><name sortKey="Kapral, G J" uniqKey="Kapral G">G.J. Kapral</name></author><author><name sortKey="Murray, L W" uniqKey="Murray L">L.W. Murray</name></author><author><name sortKey="Richardson, J S" uniqKey="Richardson J">J.S. Richardson</name></author><author><name sortKey="Richardson, D C" uniqKey="Richardson D">D.C. Richardson</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Potterton, L" uniqKey="Potterton L">L. Potterton</name></author><author><name sortKey="Mcnicholas, S" uniqKey="Mcnicholas S">S. McNicholas</name></author><author><name sortKey="Krissinel, E" uniqKey="Krissinel E">E. Krissinel</name></author><author><name sortKey="Gruber, J" uniqKey="Gruber J">J. Gruber</name></author><author><name sortKey="Cowlan, K" uniqKey="Cowlan K">K. Cowlan</name></author><author><name sortKey="Emlsey, P" uniqKey="Emlsey P">P. Emlsey</name></author><author><name sortKey="Murshudov, G N" uniqKey="Murshudov G">G.N. Murshudov</name></author><author><name sortKey="Cohen, S" uniqKey="Cohen S">S. Cohen</name></author><author><name sortKey="Perrakis, A" uniqKey="Perrakis A">A. Perrakis</name></author><author><name sortKey="Noble, M" uniqKey="Noble M">M. Noble</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Evans, P" uniqKey="Evans P">P. Evans</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Diederichs, K" uniqKey="Diederichs K">K. Diederichs</name></author><author><name sortKey="Karplus, P A" uniqKey="Karplus P">P.A. Karplus</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Weiss, M S" uniqKey="Weiss M">M.S. Weiss</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Karplus, P A" uniqKey="Karplus P">P.A. Karplus</name></author><author><name sortKey="Diederichs, K" uniqKey="Diederichs K">K. Diederichs</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Evans, P" uniqKey="Evans P">P. Evans</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Afonine, P V" uniqKey="Afonine P">P.V. Afonine</name></author><author><name sortKey="Grosse Kunstleve, R W" uniqKey="Grosse Kunstleve R">R.W. Grosse-Kunstleve</name></author><author><name sortKey="Echols, N" uniqKey="Echols N">N. Echols</name></author><author><name sortKey="Headd, J J" uniqKey="Headd J">J.J. Headd</name></author><author><name sortKey="Moriarty, N W" uniqKey="Moriarty N">N.W. Moriarty</name></author><author><name sortKey="Mustyakimov, N" uniqKey="Mustyakimov N">N. Mustyakimov</name></author><author><name sortKey="Terwilliger, T C" uniqKey="Terwilliger T">T.C. Terwilliger</name></author><author><name sortKey="Urzhumtsev, A" uniqKey="Urzhumtsev A">A. Urzhumtsev</name></author><author><name sortKey="Zwart, P H" uniqKey="Zwart P">P.H. Zwart</name></author><author><name sortKey="Adams, P D" uniqKey="Adams P">P.D. Adams</name></author></analytic></biblStruct></listBibl></div1></back></TEI><affiliations><list><country><li>États-Unis</li></country><region><li>Illinois</li><li>Iowa</li><li>Kansas</li></region><settlement><li>Iowa City</li><li>Lawrence (Kansas)</li></settlement><orgName><li>Université de l'Iowa</li><li>Université du Kansas</li></orgName></list><tree><country name="États-Unis"><region name="Kansas"><name sortKey="Galasiti Kankanamalage, Anushka C" sort="Galasiti Kankanamalage, Anushka C" uniqKey="Galasiti Kankanamalage A" first="Anushka C." last="Galasiti Kankanamalage">Anushka C. Galasiti Kankanamalage</name></region><name sortKey="Battaile, Kevin P" sort="Battaile, Kevin P" uniqKey="Battaile K" first="Kevin P." last="Battaile">Kevin P. Battaile</name><name sortKey="Chang, Kyeong Ok" sort="Chang, Kyeong Ok" uniqKey="Chang K" first="Kyeong-Ok" last="Chang">Kyeong-Ok Chang</name><name sortKey="Damalanka, Vishnu C" sort="Damalanka, Vishnu C" uniqKey="Damalanka V" first="Vishnu C." last="Damalanka">Vishnu C. Damalanka</name><name sortKey="Fehr, Anthony R" sort="Fehr, Anthony R" uniqKey="Fehr A" first="Anthony R." last="Fehr">Anthony R. Fehr</name><name sortKey="Groutas, William C" sort="Groutas, William C" uniqKey="Groutas W" first="William C." last="Groutas">William C. Groutas</name><name sortKey="Kim, Yunjeong" sort="Kim, Yunjeong" uniqKey="Kim Y" first="Yunjeong" last="Kim">Yunjeong Kim</name><name sortKey="Lovell, Scott" sort="Lovell, Scott" uniqKey="Lovell S" first="Scott" last="Lovell">Scott Lovell</name><name sortKey="Lushington, Gerald H" sort="Lushington, Gerald H" uniqKey="Lushington G" first="Gerald H." last="Lushington">Gerald H. Lushington</name><name sortKey="Mehzabeen, Nurjahan" sort="Mehzabeen, Nurjahan" uniqKey="Mehzabeen N" first="Nurjahan" last="Mehzabeen">Nurjahan Mehzabeen</name><name sortKey="Perlman, Stanley" sort="Perlman, Stanley" uniqKey="Perlman S" first="Stanley" last="Perlman">Stanley Perlman</name><name sortKey="Rathnayake, Athri D" sort="Rathnayake, Athri D" uniqKey="Rathnayake A" first="Athri D." last="Rathnayake">Athri D. Rathnayake</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
EXPLOR_STEP=$WICRI_ROOT/Sante/explor/MersV1/Data/Main/Exploration
HfdSelect -h $EXPLOR_STEP/biblio.hfd -nk 000795 | SxmlIndent | more
Ou
HfdSelect -h $EXPLOR_AREA/Data/Main/Exploration/biblio.hfd -nk 000795 | SxmlIndent | more
Pour mettre un lien sur cette page dans le réseau Wicri
{{Explor lien
|wiki= Sante
|area= MersV1
|flux= Main
|étape= Exploration
|type= RBID
|clé= PMC:5891363
|texte= Structure-guided design of potent and permeable inhibitors of MERS coronavirus 3CL protease that utilize a piperidine moiety as a novel design element
}}
Pour générer des pages wiki
HfdIndexSelect -h $EXPLOR_AREA/Data/Main/Exploration/RBID.i -Sk "pubmed:29544147" \
| HfdSelect -Kh $EXPLOR_AREA/Data/Main/Exploration/biblio.hfd \
| NlmPubMed2Wicri -a MersV1
| This area was generated with Dilib version V0.6.33. |  |