Ligand-induced Dimerization of Middle East Respiratory Syndrome (MERS) Coronavirus nsp5 Protease (3CLpro): IMPLICATIONS FOR nsp5 REGULATION AND THE DEVELOPMENT OF ANTIVIRALS.
Identifieur interne : 000E10 ( PubMed/Corpus ); précédent : 000E09; suivant : 000E11Ligand-induced Dimerization of Middle East Respiratory Syndrome (MERS) Coronavirus nsp5 Protease (3CLpro): IMPLICATIONS FOR nsp5 REGULATION AND THE DEVELOPMENT OF ANTIVIRALS.
Auteurs : Sakshi Tomar ; Melanie L. Johnston ; Sarah E. St John ; Heather L. Osswald ; Prasanth R. Nyalapatla ; Lake N. Paul ; Arun K. Ghosh ; Mark R. Denison ; Andrew D. MesecarSource :
- The Journal of biological chemistry [ 1083-351X ] ; 2015.
English descriptors
- KwdEn :
- Amino Acid Sequence, Antiviral Agents (chemical synthesis), Antiviral Agents (chemistry), Antiviral Agents (pharmacology), Crystallography, X-Ray, Cysteine Endopeptidases (chemistry), Cysteine Endopeptidases (genetics), Cysteine Endopeptidases (metabolism), Escherichia coli (genetics), Escherichia coli (metabolism), Gene Expression, Hydrophobic and Hydrophilic Interactions, Kinetics, Ligands, Middle East Respiratory Syndrome Coronavirus (drug effects), Middle East Respiratory Syndrome Coronavirus (enzymology), Middle East Respiratory Syndrome Coronavirus (genetics), Molecular Docking Simulation, Molecular Sequence Data, Peptidomimetics (chemical synthesis), Peptidomimetics (chemistry), Peptidomimetics (pharmacology), Protein Multimerization (drug effects), Recombinant Proteins (chemistry), Recombinant Proteins (genetics), Recombinant Proteins (metabolism), Sequence Alignment, Substrate Specificity, Viral Proteins (antagonists & inhibitors), Viral Proteins (chemistry), Viral Proteins (genetics), Viral Proteins (metabolism).
- MESH :
- chemical , antagonists & inhibitors : Viral Proteins.
- chemical , chemical synthesis : Antiviral Agents, Peptidomimetics.
- chemical , chemistry : Antiviral Agents, Cysteine Endopeptidases, Peptidomimetics, Recombinant Proteins, Viral Proteins.
- chemical , genetics : Cysteine Endopeptidases, Recombinant Proteins, Viral Proteins.
- chemical , metabolism : Cysteine Endopeptidases, Recombinant Proteins, Viral Proteins.
- chemical , pharmacology : Antiviral Agents, Peptidomimetics.
- drug effects : Middle East Respiratory Syndrome Coronavirus, Protein Multimerization.
- enzymology : Middle East Respiratory Syndrome Coronavirus.
- genetics : Escherichia coli, Middle East Respiratory Syndrome Coronavirus.
- metabolism : Escherichia coli.
- Amino Acid Sequence, Crystallography, X-Ray, Gene Expression, Hydrophobic and Hydrophilic Interactions, Kinetics, Ligands, Molecular Docking Simulation, Molecular Sequence Data, Sequence Alignment, Substrate Specificity.
Abstract
All coronaviruses, including the recently emerged Middle East respiratory syndrome coronavirus (MERS-CoV) from the β-CoV subgroup, require the proteolytic activity of the nsp5 protease (also known as 3C-like protease, 3CL(pro)) during virus replication, making it a high value target for the development of anti-coronavirus therapeutics. Kinetic studies indicate that in contrast to 3CL(pro) from other β-CoV 2c members, including HKU4 and HKU5, MERS-CoV 3CL(pro) is less efficient at processing a peptide substrate due to MERS-CoV 3CL(pro) being a weakly associated dimer. Conversely, HKU4, HKU5, and SARS-CoV 3CL(pro) enzymes are tightly associated dimers. Analytical ultracentrifugation studies support that MERS-CoV 3CL(pro) is a weakly associated dimer (Kd ∼52 μm) with a slow off-rate. Peptidomimetic inhibitors of MERS-CoV 3CL(pro) were synthesized and utilized in analytical ultracentrifugation experiments and demonstrate that MERS-CoV 3CL(pro) undergoes significant ligand-induced dimerization. Kinetic studies also revealed that designed reversible inhibitors act as activators at a low compound concentration as a result of induced dimerization. Primary sequence comparisons and x-ray structural analyses of two MERS-CoV 3CLpro and inhibitor complexes, determined to 1.6 Å, reveal remarkable structural similarity of the dimer interface with 3CL(pro) from HKU4-CoV and HKU5-CoV. Despite this structural similarity, substantial differences in the dimerization ability suggest that long range interactions by the nonconserved amino acids distant from the dimer interface may control MERS-CoV 3CL(pro) dimerization. Activation of MERS-CoV 3CL(pro) through ligand-induced dimerization appears to be unique within the genogroup 2c and may potentially increase the complexity in the development of MERS-CoV 3CL(pro) inhibitors as antiviral agents.
DOI: 10.1074/jbc.M115.651463
PubMed: 26055715
Links to Exploration step
pubmed:26055715Le document en format XML
<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">Ligand-induced Dimerization of Middle East Respiratory Syndrome (MERS) Coronavirus nsp5 Protease (3CLpro): IMPLICATIONS FOR nsp5 REGULATION AND THE DEVELOPMENT OF ANTIVIRALS.</title>
<author><name sortKey="Tomar, Sakshi" sort="Tomar, Sakshi" uniqKey="Tomar S" first="Sakshi" last="Tomar">Sakshi Tomar</name>
<affiliation><nlm:affiliation>From the Departments of Biological Sciences and.</nlm:affiliation>
</affiliation>
</author>
<author><name sortKey="Johnston, Melanie L" sort="Johnston, Melanie L" uniqKey="Johnston M" first="Melanie L" last="Johnston">Melanie L. Johnston</name>
<affiliation><nlm:affiliation>Chemistry, Purdue University, West Lafayette, Indiana 47907.</nlm:affiliation>
</affiliation>
</author>
<author><name sortKey="St John, Sarah E" sort="St John, Sarah E" uniqKey="St John S" first="Sarah E" last="St John">Sarah E. St John</name>
<affiliation><nlm:affiliation>From the Departments of Biological Sciences and.</nlm:affiliation>
</affiliation>
</author>
<author><name sortKey="Osswald, Heather L" sort="Osswald, Heather L" uniqKey="Osswald H" first="Heather L" last="Osswald">Heather L. Osswald</name>
<affiliation><nlm:affiliation>Chemistry, Purdue University, West Lafayette, Indiana 47907.</nlm:affiliation>
</affiliation>
</author>
<author><name sortKey="Nyalapatla, Prasanth R" sort="Nyalapatla, Prasanth R" uniqKey="Nyalapatla P" first="Prasanth R" last="Nyalapatla">Prasanth R. Nyalapatla</name>
<affiliation><nlm:affiliation>Chemistry, Purdue University, West Lafayette, Indiana 47907.</nlm:affiliation>
</affiliation>
</author>
<author><name sortKey="Paul, Lake N" sort="Paul, Lake N" uniqKey="Paul L" first="Lake N" last="Paul">Lake N. Paul</name>
<affiliation><nlm:affiliation>the Bindley Bioscience Center, Purdue University, West Lafayette, Indiana 47907, and.</nlm:affiliation>
</affiliation>
</author>
<author><name sortKey="Ghosh, Arun K" sort="Ghosh, Arun K" uniqKey="Ghosh A" first="Arun K" last="Ghosh">Arun K. Ghosh</name>
<affiliation><nlm:affiliation>Chemistry, Purdue University, West Lafayette, Indiana 47907.</nlm:affiliation>
</affiliation>
</author>
<author><name sortKey="Denison, Mark R" sort="Denison, Mark R" uniqKey="Denison M" first="Mark R" last="Denison">Mark R. Denison</name>
<affiliation><nlm:affiliation>the Departments of Pediatrics and Pathology, Microbiology and Immunology, Vanderbilt University Medical Center, Nashville, Tennessee 37232.</nlm:affiliation>
</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><nlm:affiliation>From the Departments of Biological Sciences and Chemistry, Purdue University, West Lafayette, Indiana 47907, amesecar@purdue.edu.</nlm:affiliation>
</affiliation>
</author>
</titleStmt>
<publicationStmt><idno type="wicri:source">PubMed</idno>
<date when="2015">2015</date>
<idno type="RBID">pubmed:26055715</idno>
<idno type="pmid">26055715</idno>
<idno type="doi">10.1074/jbc.M115.651463</idno>
<idno type="wicri:Area/PubMed/Corpus">000E10</idno>
<idno type="wicri:explorRef" wicri:stream="PubMed" wicri:step="Corpus" wicri:corpus="PubMed">000E10</idno>
</publicationStmt>
<sourceDesc><biblStruct><analytic><title xml:lang="en">Ligand-induced Dimerization of Middle East Respiratory Syndrome (MERS) Coronavirus nsp5 Protease (3CLpro): IMPLICATIONS FOR nsp5 REGULATION AND THE DEVELOPMENT OF ANTIVIRALS.</title>
<author><name sortKey="Tomar, Sakshi" sort="Tomar, Sakshi" uniqKey="Tomar S" first="Sakshi" last="Tomar">Sakshi Tomar</name>
<affiliation><nlm:affiliation>From the Departments of Biological Sciences and.</nlm:affiliation>
</affiliation>
</author>
<author><name sortKey="Johnston, Melanie L" sort="Johnston, Melanie L" uniqKey="Johnston M" first="Melanie L" last="Johnston">Melanie L. Johnston</name>
<affiliation><nlm:affiliation>Chemistry, Purdue University, West Lafayette, Indiana 47907.</nlm:affiliation>
</affiliation>
</author>
<author><name sortKey="St John, Sarah E" sort="St John, Sarah E" uniqKey="St John S" first="Sarah E" last="St John">Sarah E. St John</name>
<affiliation><nlm:affiliation>From the Departments of Biological Sciences and.</nlm:affiliation>
</affiliation>
</author>
<author><name sortKey="Osswald, Heather L" sort="Osswald, Heather L" uniqKey="Osswald H" first="Heather L" last="Osswald">Heather L. Osswald</name>
<affiliation><nlm:affiliation>Chemistry, Purdue University, West Lafayette, Indiana 47907.</nlm:affiliation>
</affiliation>
</author>
<author><name sortKey="Nyalapatla, Prasanth R" sort="Nyalapatla, Prasanth R" uniqKey="Nyalapatla P" first="Prasanth R" last="Nyalapatla">Prasanth R. Nyalapatla</name>
<affiliation><nlm:affiliation>Chemistry, Purdue University, West Lafayette, Indiana 47907.</nlm:affiliation>
</affiliation>
</author>
<author><name sortKey="Paul, Lake N" sort="Paul, Lake N" uniqKey="Paul L" first="Lake N" last="Paul">Lake N. Paul</name>
<affiliation><nlm:affiliation>the Bindley Bioscience Center, Purdue University, West Lafayette, Indiana 47907, and.</nlm:affiliation>
</affiliation>
</author>
<author><name sortKey="Ghosh, Arun K" sort="Ghosh, Arun K" uniqKey="Ghosh A" first="Arun K" last="Ghosh">Arun K. Ghosh</name>
<affiliation><nlm:affiliation>Chemistry, Purdue University, West Lafayette, Indiana 47907.</nlm:affiliation>
</affiliation>
</author>
<author><name sortKey="Denison, Mark R" sort="Denison, Mark R" uniqKey="Denison M" first="Mark R" last="Denison">Mark R. Denison</name>
<affiliation><nlm:affiliation>the Departments of Pediatrics and Pathology, Microbiology and Immunology, Vanderbilt University Medical Center, Nashville, Tennessee 37232.</nlm:affiliation>
</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><nlm:affiliation>From the Departments of Biological Sciences and Chemistry, Purdue University, West Lafayette, Indiana 47907, amesecar@purdue.edu.</nlm:affiliation>
</affiliation>
</author>
</analytic>
<series><title level="j">The Journal of biological chemistry</title>
<idno type="eISSN">1083-351X</idno>
<imprint><date when="2015" type="published">2015</date>
</imprint>
</series>
</biblStruct>
</sourceDesc>
</fileDesc>
<profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Amino Acid Sequence</term>
<term>Antiviral Agents (chemical synthesis)</term>
<term>Antiviral Agents (chemistry)</term>
<term>Antiviral Agents (pharmacology)</term>
<term>Crystallography, X-Ray</term>
<term>Cysteine Endopeptidases (chemistry)</term>
<term>Cysteine Endopeptidases (genetics)</term>
<term>Cysteine Endopeptidases (metabolism)</term>
<term>Escherichia coli (genetics)</term>
<term>Escherichia coli (metabolism)</term>
<term>Gene Expression</term>
<term>Hydrophobic and Hydrophilic Interactions</term>
<term>Kinetics</term>
<term>Ligands</term>
<term>Middle East Respiratory Syndrome Coronavirus (drug effects)</term>
<term>Middle East Respiratory Syndrome Coronavirus (enzymology)</term>
<term>Middle East Respiratory Syndrome Coronavirus (genetics)</term>
<term>Molecular Docking Simulation</term>
<term>Molecular Sequence Data</term>
<term>Peptidomimetics (chemical synthesis)</term>
<term>Peptidomimetics (chemistry)</term>
<term>Peptidomimetics (pharmacology)</term>
<term>Protein Multimerization (drug effects)</term>
<term>Recombinant Proteins (chemistry)</term>
<term>Recombinant Proteins (genetics)</term>
<term>Recombinant Proteins (metabolism)</term>
<term>Sequence Alignment</term>
<term>Substrate Specificity</term>
<term>Viral Proteins (antagonists & inhibitors)</term>
<term>Viral Proteins (chemistry)</term>
<term>Viral Proteins (genetics)</term>
<term>Viral Proteins (metabolism)</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>Peptidomimetics</term>
</keywords>
<keywords scheme="MESH" type="chemical" qualifier="chemistry" xml:lang="en"><term>Antiviral Agents</term>
<term>Cysteine Endopeptidases</term>
<term>Peptidomimetics</term>
<term>Recombinant Proteins</term>
<term>Viral Proteins</term>
</keywords>
<keywords scheme="MESH" type="chemical" qualifier="genetics" xml:lang="en"><term>Cysteine Endopeptidases</term>
<term>Recombinant Proteins</term>
<term>Viral Proteins</term>
</keywords>
<keywords scheme="MESH" type="chemical" qualifier="metabolism" xml:lang="en"><term>Cysteine Endopeptidases</term>
<term>Recombinant Proteins</term>
<term>Viral Proteins</term>
</keywords>
<keywords scheme="MESH" type="chemical" qualifier="pharmacology" xml:lang="en"><term>Antiviral Agents</term>
<term>Peptidomimetics</term>
</keywords>
<keywords scheme="MESH" qualifier="drug effects" xml:lang="en"><term>Middle East Respiratory Syndrome Coronavirus</term>
<term>Protein Multimerization</term>
</keywords>
<keywords scheme="MESH" qualifier="enzymology" xml:lang="en"><term>Middle East Respiratory Syndrome Coronavirus</term>
</keywords>
<keywords scheme="MESH" qualifier="genetics" xml:lang="en"><term>Escherichia coli</term>
<term>Middle East Respiratory Syndrome Coronavirus</term>
</keywords>
<keywords scheme="MESH" qualifier="metabolism" xml:lang="en"><term>Escherichia coli</term>
</keywords>
<keywords scheme="MESH" xml:lang="en"><term>Amino Acid Sequence</term>
<term>Crystallography, X-Ray</term>
<term>Gene Expression</term>
<term>Hydrophobic and Hydrophilic Interactions</term>
<term>Kinetics</term>
<term>Ligands</term>
<term>Molecular Docking Simulation</term>
<term>Molecular Sequence Data</term>
<term>Sequence Alignment</term>
<term>Substrate Specificity</term>
</keywords>
</textClass>
</profileDesc>
</teiHeader>
<front><div type="abstract" xml:lang="en">All coronaviruses, including the recently emerged Middle East respiratory syndrome coronavirus (MERS-CoV) from the β-CoV subgroup, require the proteolytic activity of the nsp5 protease (also known as 3C-like protease, 3CL(pro)) during virus replication, making it a high value target for the development of anti-coronavirus therapeutics. Kinetic studies indicate that in contrast to 3CL(pro) from other β-CoV 2c members, including HKU4 and HKU5, MERS-CoV 3CL(pro) is less efficient at processing a peptide substrate due to MERS-CoV 3CL(pro) being a weakly associated dimer. Conversely, HKU4, HKU5, and SARS-CoV 3CL(pro) enzymes are tightly associated dimers. Analytical ultracentrifugation studies support that MERS-CoV 3CL(pro) is a weakly associated dimer (Kd ∼52 μm) with a slow off-rate. Peptidomimetic inhibitors of MERS-CoV 3CL(pro) were synthesized and utilized in analytical ultracentrifugation experiments and demonstrate that MERS-CoV 3CL(pro) undergoes significant ligand-induced dimerization. Kinetic studies also revealed that designed reversible inhibitors act as activators at a low compound concentration as a result of induced dimerization. Primary sequence comparisons and x-ray structural analyses of two MERS-CoV 3CLpro and inhibitor complexes, determined to 1.6 Å, reveal remarkable structural similarity of the dimer interface with 3CL(pro) from HKU4-CoV and HKU5-CoV. Despite this structural similarity, substantial differences in the dimerization ability suggest that long range interactions by the nonconserved amino acids distant from the dimer interface may control MERS-CoV 3CL(pro) dimerization. Activation of MERS-CoV 3CL(pro) through ligand-induced dimerization appears to be unique within the genogroup 2c and may potentially increase the complexity in the development of MERS-CoV 3CL(pro) inhibitors as antiviral agents. </div>
</front>
</TEI>
<pubmed><MedlineCitation Status="MEDLINE" Owner="NLM"><PMID Version="1">26055715</PMID>
<DateCompleted><Year>2015</Year>
<Month>11</Month>
<Day>05</Day>
</DateCompleted>
<DateRevised><Year>2020</Year>
<Month>03</Month>
<Day>28</Day>
</DateRevised>
<Article PubModel="Print-Electronic"><Journal><ISSN IssnType="Electronic">1083-351X</ISSN>
<JournalIssue CitedMedium="Internet"><Volume>290</Volume>
<Issue>32</Issue>
<PubDate><Year>2015</Year>
<Month>Aug</Month>
<Day>07</Day>
</PubDate>
</JournalIssue>
<Title>The Journal of biological chemistry</Title>
<ISOAbbreviation>J. Biol. Chem.</ISOAbbreviation>
</Journal>
<ArticleTitle>Ligand-induced Dimerization of Middle East Respiratory Syndrome (MERS) Coronavirus nsp5 Protease (3CLpro): IMPLICATIONS FOR nsp5 REGULATION AND THE DEVELOPMENT OF ANTIVIRALS.</ArticleTitle>
<Pagination><MedlinePgn>19403-22</MedlinePgn>
</Pagination>
<ELocationID EIdType="doi" ValidYN="Y">10.1074/jbc.M115.651463</ELocationID>
<Abstract><AbstractText>All coronaviruses, including the recently emerged Middle East respiratory syndrome coronavirus (MERS-CoV) from the β-CoV subgroup, require the proteolytic activity of the nsp5 protease (also known as 3C-like protease, 3CL(pro)) during virus replication, making it a high value target for the development of anti-coronavirus therapeutics. Kinetic studies indicate that in contrast to 3CL(pro) from other β-CoV 2c members, including HKU4 and HKU5, MERS-CoV 3CL(pro) is less efficient at processing a peptide substrate due to MERS-CoV 3CL(pro) being a weakly associated dimer. Conversely, HKU4, HKU5, and SARS-CoV 3CL(pro) enzymes are tightly associated dimers. Analytical ultracentrifugation studies support that MERS-CoV 3CL(pro) is a weakly associated dimer (Kd ∼52 μm) with a slow off-rate. Peptidomimetic inhibitors of MERS-CoV 3CL(pro) were synthesized and utilized in analytical ultracentrifugation experiments and demonstrate that MERS-CoV 3CL(pro) undergoes significant ligand-induced dimerization. Kinetic studies also revealed that designed reversible inhibitors act as activators at a low compound concentration as a result of induced dimerization. Primary sequence comparisons and x-ray structural analyses of two MERS-CoV 3CLpro and inhibitor complexes, determined to 1.6 Å, reveal remarkable structural similarity of the dimer interface with 3CL(pro) from HKU4-CoV and HKU5-CoV. Despite this structural similarity, substantial differences in the dimerization ability suggest that long range interactions by the nonconserved amino acids distant from the dimer interface may control MERS-CoV 3CL(pro) dimerization. Activation of MERS-CoV 3CL(pro) through ligand-induced dimerization appears to be unique within the genogroup 2c and may potentially increase the complexity in the development of MERS-CoV 3CL(pro) inhibitors as antiviral agents. </AbstractText>
<CopyrightInformation>© 2015 by The American Society for Biochemistry and Molecular Biology, Inc.</CopyrightInformation>
</Abstract>
<AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Tomar</LastName>
<ForeName>Sakshi</ForeName>
<Initials>S</Initials>
<AffiliationInfo><Affiliation>From the Departments of Biological Sciences and.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Johnston</LastName>
<ForeName>Melanie L</ForeName>
<Initials>ML</Initials>
<AffiliationInfo><Affiliation>Chemistry, Purdue University, West Lafayette, Indiana 47907.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>St John</LastName>
<ForeName>Sarah E</ForeName>
<Initials>SE</Initials>
<AffiliationInfo><Affiliation>From the Departments of Biological Sciences and.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Osswald</LastName>
<ForeName>Heather L</ForeName>
<Initials>HL</Initials>
<AffiliationInfo><Affiliation>Chemistry, Purdue University, West Lafayette, Indiana 47907.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Nyalapatla</LastName>
<ForeName>Prasanth R</ForeName>
<Initials>PR</Initials>
<AffiliationInfo><Affiliation>Chemistry, Purdue University, West Lafayette, Indiana 47907.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Paul</LastName>
<ForeName>Lake N</ForeName>
<Initials>LN</Initials>
<AffiliationInfo><Affiliation>the Bindley Bioscience Center, Purdue University, West Lafayette, Indiana 47907, and.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Ghosh</LastName>
<ForeName>Arun K</ForeName>
<Initials>AK</Initials>
<AffiliationInfo><Affiliation>Chemistry, Purdue University, West Lafayette, Indiana 47907.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Denison</LastName>
<ForeName>Mark R</ForeName>
<Initials>MR</Initials>
<AffiliationInfo><Affiliation>the Departments of Pediatrics and Pathology, Microbiology and Immunology, Vanderbilt University Medical Center, Nashville, Tennessee 37232.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Mesecar</LastName>
<ForeName>Andrew D</ForeName>
<Initials>AD</Initials>
<AffiliationInfo><Affiliation>From the Departments of Biological Sciences and Chemistry, Purdue University, West Lafayette, Indiana 47907, amesecar@purdue.edu.</Affiliation>
</AffiliationInfo>
</Author>
</AuthorList>
<Language>eng</Language>
<DataBankList CompleteYN="Y"><DataBank><DataBankName>PDB</DataBankName>
<AccessionNumberList><AccessionNumber>2ALV</AccessionNumber>
<AccessionNumber>2YNB</AccessionNumber>
<AccessionNumber>3V3M</AccessionNumber>
<AccessionNumber>4MDS</AccessionNumber>
<AccessionNumber>4RSP</AccessionNumber>
<AccessionNumber>4YLU</AccessionNumber>
</AccessionNumberList>
</DataBank>
</DataBankList>
<GrantList CompleteYN="Y"><Grant><GrantID>R01 AI026603</GrantID>
<Acronym>AI</Acronym>
<Agency>NIAID NIH HHS</Agency>
<Country>United States</Country>
</Grant>
<Grant><GrantID>AI08508</GrantID>
<Acronym>AI</Acronym>
<Agency>NIAID NIH HHS</Agency>
<Country>United States</Country>
</Grant>
<Grant><GrantID>AI026603</GrantID>
<Acronym>AI</Acronym>
<Agency>NIAID NIH HHS</Agency>
<Country>United States</Country>
</Grant>
<Grant><GrantID>P30 CA023168</GrantID>
<Acronym>CA</Acronym>
<Agency>NCI NIH HHS</Agency>
<Country>United States</Country>
</Grant>
<Grant><GrantID>R37 GM053386</GrantID>
<Acronym>GM</Acronym>
<Agency>NIGMS NIH HHS</Agency>
<Country>United States</Country>
</Grant>
</GrantList>
<PublicationTypeList><PublicationType UI="D016428">Journal Article</PublicationType>
<PublicationType UI="D052061">Research Support, N.I.H., Extramural</PublicationType>
<PublicationType UI="D013485">Research Support, Non-U.S. Gov't</PublicationType>
<PublicationType UI="D013486">Research Support, U.S. Gov't, Non-P.H.S.</PublicationType>
</PublicationTypeList>
<ArticleDate DateType="Electronic"><Year>2015</Year>
<Month>06</Month>
<Day>08</Day>
</ArticleDate>
</Article>
<MedlineJournalInfo><Country>United States</Country>
<MedlineTA>J Biol Chem</MedlineTA>
<NlmUniqueID>2985121R</NlmUniqueID>
<ISSNLinking>0021-9258</ISSNLinking>
</MedlineJournalInfo>
<ChemicalList><Chemical><RegistryNumber>0</RegistryNumber>
<NameOfSubstance UI="D000998">Antiviral Agents</NameOfSubstance>
</Chemical>
<Chemical><RegistryNumber>0</RegistryNumber>
<NameOfSubstance UI="D008024">Ligands</NameOfSubstance>
</Chemical>
<Chemical><RegistryNumber>0</RegistryNumber>
<NameOfSubstance UI="D057786">Peptidomimetics</NameOfSubstance>
</Chemical>
<Chemical><RegistryNumber>0</RegistryNumber>
<NameOfSubstance UI="D011994">Recombinant Proteins</NameOfSubstance>
</Chemical>
<Chemical><RegistryNumber>0</RegistryNumber>
<NameOfSubstance UI="D014764">Viral Proteins</NameOfSubstance>
</Chemical>
<Chemical><RegistryNumber>EC 3.4.22.-</RegistryNumber>
<NameOfSubstance UI="C099456">3C-like proteinase, Coronavirus</NameOfSubstance>
</Chemical>
<Chemical><RegistryNumber>EC 3.4.22.-</RegistryNumber>
<NameOfSubstance UI="D003546">Cysteine Endopeptidases</NameOfSubstance>
</Chemical>
</ChemicalList>
<CitationSubset>IM</CitationSubset>
<MeshHeadingList><MeshHeading><DescriptorName UI="D000595" MajorTopicYN="N">Amino Acid Sequence</DescriptorName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D000998" MajorTopicYN="N">Antiviral Agents</DescriptorName>
<QualifierName UI="Q000138" MajorTopicYN="N">chemical synthesis</QualifierName>
<QualifierName UI="Q000737" MajorTopicYN="Y">chemistry</QualifierName>
<QualifierName UI="Q000494" MajorTopicYN="N">pharmacology</QualifierName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D018360" MajorTopicYN="N">Crystallography, X-Ray</DescriptorName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D003546" MajorTopicYN="N">Cysteine Endopeptidases</DescriptorName>
<QualifierName UI="Q000737" MajorTopicYN="Y">chemistry</QualifierName>
<QualifierName UI="Q000235" MajorTopicYN="N">genetics</QualifierName>
<QualifierName UI="Q000378" MajorTopicYN="N">metabolism</QualifierName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D004926" MajorTopicYN="N">Escherichia coli</DescriptorName>
<QualifierName UI="Q000235" MajorTopicYN="N">genetics</QualifierName>
<QualifierName UI="Q000378" MajorTopicYN="N">metabolism</QualifierName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D015870" MajorTopicYN="N">Gene Expression</DescriptorName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D057927" MajorTopicYN="N">Hydrophobic and Hydrophilic Interactions</DescriptorName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D007700" MajorTopicYN="N">Kinetics</DescriptorName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D008024" MajorTopicYN="N">Ligands</DescriptorName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D065207" MajorTopicYN="N">Middle East Respiratory Syndrome Coronavirus</DescriptorName>
<QualifierName UI="Q000187" MajorTopicYN="Y">drug effects</QualifierName>
<QualifierName UI="Q000201" MajorTopicYN="N">enzymology</QualifierName>
<QualifierName UI="Q000235" MajorTopicYN="N">genetics</QualifierName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D062105" MajorTopicYN="N">Molecular Docking Simulation</DescriptorName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D008969" MajorTopicYN="N">Molecular Sequence Data</DescriptorName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D057786" MajorTopicYN="N">Peptidomimetics</DescriptorName>
<QualifierName UI="Q000138" MajorTopicYN="N">chemical synthesis</QualifierName>
<QualifierName UI="Q000737" MajorTopicYN="Y">chemistry</QualifierName>
<QualifierName UI="Q000494" MajorTopicYN="N">pharmacology</QualifierName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D055503" MajorTopicYN="N">Protein Multimerization</DescriptorName>
<QualifierName UI="Q000187" MajorTopicYN="Y">drug effects</QualifierName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D011994" MajorTopicYN="N">Recombinant Proteins</DescriptorName>
<QualifierName UI="Q000737" MajorTopicYN="N">chemistry</QualifierName>
<QualifierName UI="Q000235" MajorTopicYN="N">genetics</QualifierName>
<QualifierName UI="Q000378" MajorTopicYN="N">metabolism</QualifierName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D016415" MajorTopicYN="N">Sequence Alignment</DescriptorName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D013379" MajorTopicYN="N">Substrate Specificity</DescriptorName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D014764" MajorTopicYN="N">Viral Proteins</DescriptorName>
<QualifierName UI="Q000037" MajorTopicYN="N">antagonists & inhibitors</QualifierName>
<QualifierName UI="Q000737" MajorTopicYN="Y">chemistry</QualifierName>
<QualifierName UI="Q000235" MajorTopicYN="N">genetics</QualifierName>
<QualifierName UI="Q000378" MajorTopicYN="N">metabolism</QualifierName>
</MeshHeading>
</MeshHeadingList>
<KeywordList Owner="NOTNLM"><Keyword MajorTopicYN="N">MERS-CoV 3CLpro</Keyword>
<Keyword MajorTopicYN="N">X-ray crystallography</Keyword>
<Keyword MajorTopicYN="N">analytical ultracentrifugation</Keyword>
<Keyword MajorTopicYN="N">enzyme inactivation</Keyword>
<Keyword MajorTopicYN="N">enzyme inhibitor</Keyword>
<Keyword MajorTopicYN="N">enzyme kinetics</Keyword>
<Keyword MajorTopicYN="N">ligand-induced dimerization</Keyword>
<Keyword MajorTopicYN="N">monomer-dimer equilibrium</Keyword>
<Keyword MajorTopicYN="N">viral protease</Keyword>
<Keyword MajorTopicYN="N">β-CoV</Keyword>
</KeywordList>
</MedlineCitation>
<PubmedData><History><PubMedPubDate PubStatus="received"><Year>2015</Year>
<Month>03</Month>
<Day>11</Day>
</PubMedPubDate>
<PubMedPubDate PubStatus="entrez"><Year>2015</Year>
<Month>6</Month>
<Day>10</Day>
<Hour>6</Hour>
<Minute>0</Minute>
</PubMedPubDate>
<PubMedPubDate PubStatus="pubmed"><Year>2015</Year>
<Month>6</Month>
<Day>10</Day>
<Hour>6</Hour>
<Minute>0</Minute>
</PubMedPubDate>
<PubMedPubDate PubStatus="medline"><Year>2015</Year>
<Month>11</Month>
<Day>6</Day>
<Hour>6</Hour>
<Minute>0</Minute>
</PubMedPubDate>
</History>
<PublicationStatus>ppublish</PublicationStatus>
<ArticleIdList><ArticleId IdType="pubmed">26055715</ArticleId>
<ArticleId IdType="pii">M115.651463</ArticleId>
<ArticleId IdType="doi">10.1074/jbc.M115.651463</ArticleId>
<ArticleId IdType="pmc">PMC4528106</ArticleId>
</ArticleIdList>
<ReferenceList><Reference><Citation>Protein Cell. 2010 Jan;1(1):59-74</Citation>
<ArticleIdList><ArticleId IdType="pubmed">21203998</ArticleId>
</ArticleIdList>
</Reference>
</ReferenceList>
<ReferenceList><Reference><Citation>PLoS One. 2014 Jul 18;9(7):e101941</Citation>
<ArticleIdList><ArticleId IdType="pubmed">25036652</ArticleId>
</ArticleIdList>
</Reference>
</ReferenceList>
<ReferenceList><Reference><Citation>N Engl J Med. 2012 Nov 8;367(19):1814-20</Citation>
<ArticleIdList><ArticleId IdType="pubmed">23075143</ArticleId>
</ArticleIdList>
</Reference>
</ReferenceList>
<ReferenceList><Reference><Citation>mBio. 2014 Mar 25;5(2):e00047-14</Citation>
<ArticleIdList><ArticleId IdType="pubmed">24667706</ArticleId>
</ArticleIdList>
</Reference>
</ReferenceList>
<ReferenceList><Reference><Citation>Science. 2003 Jun 13;300(5626):1763-7</Citation>
<ArticleIdList><ArticleId IdType="pubmed">12746549</ArticleId>
</ArticleIdList>
</Reference>
</ReferenceList>
<ReferenceList><Reference><Citation>Mol Cell. 2006 Jun 23;22(6):807-18</Citation>
<ArticleIdList><ArticleId IdType="pubmed">16793549</ArticleId>
</ArticleIdList>
</Reference>
</ReferenceList>
<ReferenceList><Reference><Citation>J Biol Chem. 2005 Sep 2;280(35):31257-66</Citation>
<ArticleIdList><ArticleId IdType="pubmed">15788388</ArticleId>
</ArticleIdList>
</Reference>
</ReferenceList>
<ReferenceList><Reference><Citation>Nucleic Acids Res. 1988 Nov 25;16(22):10881-90</Citation>
<ArticleIdList><ArticleId IdType="pubmed">2849754</ArticleId>
</ArticleIdList>
</Reference>
</ReferenceList>
<ReferenceList><Reference><Citation>Lancet Infect Dis. 2013 Oct;13(10):859-66</Citation>
<ArticleIdList><ArticleId IdType="pubmed">23933067</ArticleId>
</ArticleIdList>
</Reference>
</ReferenceList>
<ReferenceList><Reference><Citation>Adv Virus Res. 1997;48:1-100</Citation>
<ArticleIdList><ArticleId IdType="pubmed">9233431</ArticleId>
</ArticleIdList>
</Reference>
</ReferenceList>
<ReferenceList><Reference><Citation>J Infect. 2012 Dec;65(6):477-89</Citation>
<ArticleIdList><ArticleId IdType="pubmed">23072791</ArticleId>
</ArticleIdList>
</Reference>
</ReferenceList>
<ReferenceList><Reference><Citation>Lancet. 2013 Dec 14;382(9909):1993-2002</Citation>
<ArticleIdList><ArticleId IdType="pubmed">24055451</ArticleId>
</ArticleIdList>
</Reference>
</ReferenceList>
<ReferenceList><Reference><Citation>J Biol Chem. 2004 Jan 16;279(3):1637-42</Citation>
<ArticleIdList><ArticleId IdType="pubmed">14561748</ArticleId>
</ArticleIdList>
</Reference>
</ReferenceList>
<ReferenceList><Reference><Citation>Curr Protoc Immunol. 2008 May;Chapter 18:Unit 18.15</Citation>
<ArticleIdList><ArticleId IdType="pubmed">18491296</ArticleId>
</ArticleIdList>
</Reference>
</ReferenceList>
<ReferenceList><Reference><Citation>Acta Crystallogr D Biol Crystallogr. 2010 Jan;66(Pt 1):12-21</Citation>
<ArticleIdList><ArticleId IdType="pubmed">20057044</ArticleId>
</ArticleIdList>
</Reference>
</ReferenceList>
<ReferenceList><Reference><Citation>Chem Biol. 2004 Oct;11(10):1445-53</Citation>
<ArticleIdList><ArticleId IdType="pubmed">15489171</ArticleId>
</ArticleIdList>
</Reference>
</ReferenceList>
<ReferenceList><Reference><Citation>Lancet. 2013 Aug 24;382(9893):694-9</Citation>
<ArticleIdList><ArticleId IdType="pubmed">23831141</ArticleId>
</ArticleIdList>
</Reference>
</ReferenceList>
<ReferenceList><Reference><Citation>J Med Chem. 2005 Nov 3;48(22):6832-42</Citation>
<ArticleIdList><ArticleId IdType="pubmed">16250642</ArticleId>
</ArticleIdList>
</Reference>
</ReferenceList>
<ReferenceList><Reference><Citation>Methods Enzymol. 1997;276:307-26</Citation>
<ArticleIdList><ArticleId IdType="pubmed">27754618</ArticleId>
</ArticleIdList>
</Reference>
</ReferenceList>
<ReferenceList><Reference><Citation>J Med Chem. 2014 Mar 27;57(6):2393-412</Citation>
<ArticleIdList><ArticleId IdType="pubmed">24568342</ArticleId>
</ArticleIdList>
</Reference>
</ReferenceList>
<ReferenceList><Reference><Citation>J Biol Chem. 2010 Sep 3;285(36):28134-40</Citation>
<ArticleIdList><ArticleId IdType="pubmed">20489209</ArticleId>
</ArticleIdList>
</Reference>
</ReferenceList>
<ReferenceList><Reference><Citation>Curr Pharm Des. 2006;12(35):4555-64</Citation>
<ArticleIdList><ArticleId IdType="pubmed">17168761</ArticleId>
</ArticleIdList>
</Reference>
</ReferenceList>
<ReferenceList><Reference><Citation>Acta Crystallogr D Biol Crystallogr. 2013 May;69(Pt 5):747-55</Citation>
<ArticleIdList><ArticleId IdType="pubmed">23633583</ArticleId>
</ArticleIdList>
</Reference>
</ReferenceList>
<ReferenceList><Reference><Citation>J Gen Virol. 2000 Apr;81(Pt 4):853-79</Citation>
<ArticleIdList><ArticleId IdType="pubmed">10725411</ArticleId>
</ArticleIdList>
</Reference>
</ReferenceList>
<ReferenceList><Reference><Citation>J Med Chem. 2013 Jan 24;56(2):534-46</Citation>
<ArticleIdList><ArticleId IdType="pubmed">23231439</ArticleId>
</ArticleIdList>
</Reference>
</ReferenceList>
<ReferenceList><Reference><Citation>J Biol Chem. 2004 Jun 4;279(23):24765-73</Citation>
<ArticleIdList><ArticleId IdType="pubmed">15037623</ArticleId>
</ArticleIdList>
</Reference>
</ReferenceList>
<ReferenceList><Reference><Citation>J Virol. 2012 May;86(9):4801-10</Citation>
<ArticleIdList><ArticleId IdType="pubmed">22345451</ArticleId>
</ArticleIdList>
</Reference>
</ReferenceList>
<ReferenceList><Reference><Citation>Biochemistry. 2001 Nov 6;40(44):13230-6</Citation>
<ArticleIdList><ArticleId IdType="pubmed">11683631</ArticleId>
</ArticleIdList>
</Reference>
</ReferenceList>
<ReferenceList><Reference><Citation>J Virol. 2008 May;82(9):4620-9</Citation>
<ArticleIdList><ArticleId IdType="pubmed">18305031</ArticleId>
</ArticleIdList>
</Reference>
</ReferenceList>
<ReferenceList><Reference><Citation>Emerg Infect Dis. 2013 Nov;19(11):1819-23</Citation>
<ArticleIdList><ArticleId IdType="pubmed">24206838</ArticleId>
</ArticleIdList>
</Reference>
</ReferenceList>
<ReferenceList><Reference><Citation>Nature. 2012 Dec 13;492(7428):166-7</Citation>
<ArticleIdList><ArticleId IdType="pubmed">23235854</ArticleId>
</ArticleIdList>
</Reference>
</ReferenceList>
<ReferenceList><Reference><Citation>J Biochem. 2008 Apr;143(4):525-36</Citation>
<ArticleIdList><ArticleId IdType="pubmed">18182387</ArticleId>
</ArticleIdList>
</Reference>
</ReferenceList>
<ReferenceList><Reference><Citation>Acta Crystallogr D Biol Crystallogr. 2010 Apr;66(Pt 4):486-501</Citation>
<ArticleIdList><ArticleId IdType="pubmed">20383002</ArticleId>
</ArticleIdList>
</Reference>
</ReferenceList>
<ReferenceList><Reference><Citation>Biochemistry. 2006 Dec 19;45(50):14908-16</Citation>
<ArticleIdList><ArticleId IdType="pubmed">17154528</ArticleId>
</ArticleIdList>
</Reference>
</ReferenceList>
<ReferenceList><Reference><Citation>Proc Natl Acad Sci U S A. 1967 Dec;58(6):2268-73</Citation>
<ArticleIdList><ArticleId IdType="pubmed">4298953</ArticleId>
</ArticleIdList>
</Reference>
</ReferenceList>
<ReferenceList><Reference><Citation>Proc Natl Acad Sci U S A. 2003 Nov 11;100(23):13190-5</Citation>
<ArticleIdList><ArticleId IdType="pubmed">14585926</ArticleId>
</ArticleIdList>
</Reference>
</ReferenceList>
<ReferenceList><Reference><Citation>Emerg Infect Dis. 2013 Mar;19(3):456-9</Citation>
<ArticleIdList><ArticleId IdType="pubmed">23622767</ArticleId>
</ArticleIdList>
</Reference>
</ReferenceList>
<ReferenceList><Reference><Citation>Genome Res. 2004 Jun;14(6):1188-90</Citation>
<ArticleIdList><ArticleId IdType="pubmed">15173120</ArticleId>
</ArticleIdList>
</Reference>
</ReferenceList>
<ReferenceList><Reference><Citation>mBio. 2012 Nov 20;3(6):</Citation>
<ArticleIdList><ArticleId IdType="pubmed">23170002</ArticleId>
</ArticleIdList>
</Reference>
</ReferenceList>
<ReferenceList><Reference><Citation>Adv Virol. 2011;2011:129134</Citation>
<ArticleIdList><ArticleId IdType="pubmed">22315599</ArticleId>
</ArticleIdList>
</Reference>
</ReferenceList>
<ReferenceList><Reference><Citation>Nat Rev Microbiol. 2009 Jun;7(6):439-50</Citation>
<ArticleIdList><ArticleId IdType="pubmed">19430490</ArticleId>
</ArticleIdList>
</Reference>
</ReferenceList>
<ReferenceList><Reference><Citation>J Med Chem. 2005 Nov 3;48(22):6767-71</Citation>
<ArticleIdList><ArticleId IdType="pubmed">16250632</ArticleId>
</ArticleIdList>
</Reference>
</ReferenceList>
<ReferenceList><Reference><Citation>Bioorg Med Chem Lett. 2013 Nov 15;23(22):6172-7</Citation>
<ArticleIdList><ArticleId IdType="pubmed">24080461</ArticleId>
</ArticleIdList>
</Reference>
</ReferenceList>
<ReferenceList><Reference><Citation>Acta Vet Scand. 1991;32(2):163-70</Citation>
<ArticleIdList><ArticleId IdType="pubmed">1666489</ArticleId>
</ArticleIdList>
</Reference>
</ReferenceList>
<ReferenceList><Reference><Citation>Acta Crystallogr D Biol Crystallogr. 2010 Feb;66(Pt 2):213-21</Citation>
<ArticleIdList><ArticleId IdType="pubmed">20124702</ArticleId>
</ArticleIdList>
</Reference>
</ReferenceList>
<ReferenceList><Reference><Citation>Nat Med. 2004 Apr;10(4):368-73</Citation>
<ArticleIdList><ArticleId IdType="pubmed">15034574</ArticleId>
</ArticleIdList>
</Reference>
</ReferenceList>
<ReferenceList><Reference><Citation>N Engl J Med. 2013 Aug 1;369(5):407-16</Citation>
<ArticleIdList><ArticleId IdType="pubmed">23782161</ArticleId>
</ArticleIdList>
</Reference>
</ReferenceList>
<ReferenceList><Reference><Citation>J Virol. 2005 Jan;79(2):884-95</Citation>
<ArticleIdList><ArticleId IdType="pubmed">15613317</ArticleId>
</ArticleIdList>
</Reference>
</ReferenceList>
<ReferenceList><Reference><Citation>Bioorg Med Chem Lett. 2008 Oct 15;18(20):5684-8</Citation>
<ArticleIdList><ArticleId IdType="pubmed">18796354</ArticleId>
</ArticleIdList>
</Reference>
</ReferenceList>
<ReferenceList><Reference><Citation>J Virol. 1995 Jun;69(6):3554-9</Citation>
<ArticleIdList><ArticleId IdType="pubmed">7745703</ArticleId>
</ArticleIdList>
</Reference>
</ReferenceList>
<ReferenceList><Reference><Citation>Euro Surveill. 2013 Jun 13;18(24):</Citation>
<ArticleIdList><ArticleId IdType="pubmed">23787162</ArticleId>
</ArticleIdList>
</Reference>
</ReferenceList>
<ReferenceList><Reference><Citation>PLoS Comput Biol. 2011 Feb;7(2):e1001084</Citation>
<ArticleIdList><ArticleId IdType="pubmed">21390281</ArticleId>
</ArticleIdList>
</Reference>
</ReferenceList>
<ReferenceList><Reference><Citation>Bioorg Med Chem Lett. 2007 Nov 1;17(21):5876-80</Citation>
<ArticleIdList><ArticleId IdType="pubmed">17855091</ArticleId>
</ArticleIdList>
</Reference>
</ReferenceList>
<ReferenceList><Reference><Citation>Proc Soc Exp Biol Med. 1966 Jan;121(1):190-3</Citation>
<ArticleIdList><ArticleId IdType="pubmed">4285768</ArticleId>
</ArticleIdList>
</Reference>
</ReferenceList>
<ReferenceList><Reference><Citation>Virus Res. 2008 Apr;133(1):63-73</Citation>
<ArticleIdList><ArticleId IdType="pubmed">17397958</ArticleId>
</ArticleIdList>
</Reference>
</ReferenceList>
<ReferenceList><Reference><Citation>Curr Pharm Des. 2006;12(35):4573-90</Citation>
<ArticleIdList><ArticleId IdType="pubmed">17168763</ArticleId>
</ArticleIdList>
</Reference>
</ReferenceList>
<ReferenceList><Reference><Citation>Biophys J. 2010 Apr 7;98(7):1327-36</Citation>
<ArticleIdList><ArticleId IdType="pubmed">20371333</ArticleId>
</ArticleIdList>
</Reference>
</ReferenceList>
<ReferenceList><Reference><Citation>Vet Rec. 1985 Nov 2;117(18):459-64</Citation>
<ArticleIdList><ArticleId IdType="pubmed">3000058</ArticleId>
</ArticleIdList>
</Reference>
</ReferenceList>
<ReferenceList><Reference><Citation>J Infect Dis. 1970 Oct;122(4):272-9</Citation>
<ArticleIdList><ArticleId IdType="pubmed">5504709</ArticleId>
</ArticleIdList>
</Reference>
</ReferenceList>
<ReferenceList><Reference><Citation>Euro Surveill. 2013 Sep 05;18(36):pii=20574</Citation>
<ArticleIdList><ArticleId IdType="pubmed">24079378</ArticleId>
</ArticleIdList>
</Reference>
</ReferenceList>
<ReferenceList><Reference><Citation>Nucleic Acids Res. 2014 Jul;42(Web Server issue):W320-4</Citation>
<ArticleIdList><ArticleId IdType="pubmed">24753421</ArticleId>
</ArticleIdList>
</Reference>
</ReferenceList>
</PubmedData>
</pubmed>
</record>
Pour manipuler ce document sous Unix (Dilib)
EXPLOR_STEP=$WICRI_ROOT/Sante/explor/SrasV1/Data/PubMed/Corpus
HfdSelect -h $EXPLOR_STEP/biblio.hfd -nk 000E10 | SxmlIndent | more
Ou
HfdSelect -h $EXPLOR_AREA/Data/PubMed/Corpus/biblio.hfd -nk 000E10 | SxmlIndent | more
Pour mettre un lien sur cette page dans le réseau Wicri
{{Explor lien |wiki= Sante |area= SrasV1 |flux= PubMed |étape= Corpus |type= RBID |clé= pubmed:26055715 |texte= Ligand-induced Dimerization of Middle East Respiratory Syndrome (MERS) Coronavirus nsp5 Protease (3CLpro): IMPLICATIONS FOR nsp5 REGULATION AND THE DEVELOPMENT OF ANTIVIRALS. }}
Pour générer des pages wiki
HfdIndexSelect -h $EXPLOR_AREA/Data/PubMed/Corpus/RBID.i -Sk "pubmed:26055715" \ | HfdSelect -Kh $EXPLOR_AREA/Data/PubMed/Corpus/biblio.hfd \ | NlmPubMed2Wicri -a SrasV1
This area was generated with Dilib version V0.6.33. |