Identification and design of novel small molecule inhibitors against MERS-CoV papain-like protease via high-throughput screening and molecular modeling.
Identifieur interne : 000586 ( PubMed/Corpus ); précédent : 000585; suivant : 000587Identification and design of novel small molecule inhibitors against MERS-CoV papain-like protease via high-throughput screening and molecular modeling.
Auteurs : Hyun Lee ; Jinhong Ren ; Russell P. Pesavento ; Isabel Ojeda ; Amy J. Rice ; Haining Lv ; Youngjin Kwon ; Michael E. JohnsonSource :
- Bioorganic & medicinal chemistry [ 1464-3391 ] ; 2019.
English descriptors
- KwdEn :
- Binding Sites, Drug Design, Electron Spin Resonance Spectroscopy, High-Throughput Screening Assays, Humans, Middle East Respiratory Syndrome Coronavirus (enzymology), Molecular Docking Simulation, Peptide Hydrolases (chemistry), Peptide Hydrolases (metabolism), Protease Inhibitors (chemistry), Protease Inhibitors (metabolism), Protein Structure, Tertiary, Small Molecule Libraries (chemistry), Small Molecule Libraries (metabolism), Structure-Activity Relationship, Viral Proteins (antagonists & inhibitors), Viral Proteins (metabolism).
- MESH :
- chemical , antagonists & inhibitors : Viral Proteins.
- chemical , chemistry : Peptide Hydrolases, Protease Inhibitors, Small Molecule Libraries.
- enzymology : Middle East Respiratory Syndrome Coronavirus.
- chemical , metabolism : Peptide Hydrolases, Protease Inhibitors, Small Molecule Libraries, Viral Proteins.
- Binding Sites, Drug Design, Electron Spin Resonance Spectroscopy, High-Throughput Screening Assays, Humans, Molecular Docking Simulation, Protein Structure, Tertiary, Structure-Activity Relationship.
Abstract
The development of new therapeutic agents against the coronavirus causing Middle East Respiratory Syndrome (MERS) is a continuing imperative. The initial MERS-CoV epidemic was contained entirely through public health measures, but episodic cases continue, as there are currently no therapeutic agents effective in the treatment of MERS-CoV, although multiple strategies have been proposed. In this study, we screened 30,000 compounds from three different compound libraries against one of the essential proteases, the papain-like protease (PLpro), using a fluorescence-based enzymatic assay followed by surface plasmon resonance (SPR) direct binding analysis for hit confirmation. Mode of inhibition assays and competition SPR studies revealed two compounds to be competitive inhibitors. To improve upon the inhibitory activity of the best hit compounds, a small fragment library consisting of 352 fragments was screened in the presence of each hit compound, resulting in one fragment that enhanced the IC50 value of the best hit compound by 3-fold. Molecular docking and MM/PBSA binding energy calculations were used to predict potential binding sites, providing insight for design and synthesis of next-generation compounds.
DOI: 10.1016/j.bmc.2019.03.050
PubMed: 30940566
Links to Exploration step
pubmed:30940566Le document en format XML
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Electronic address: danielhl@uic.edu.</nlm:affiliation></affiliation></author><author><name sortKey="Ren, Jinhong" sort="Ren, Jinhong" uniqKey="Ren J" first="Jinhong" last="Ren">Jinhong Ren</name><affiliation><nlm:affiliation>Center for Biomolecular Sciences and Department of Medicinal Chemistry and Pharmacognosy, University of Illinois at Chicago, 900 S. Ashland, IL 60607, USA.</nlm:affiliation></affiliation></author><author><name sortKey="Pesavento, Russell P" sort="Pesavento, Russell P" uniqKey="Pesavento R" first="Russell P" last="Pesavento">Russell P. Pesavento</name><affiliation><nlm:affiliation>Center for Biomolecular Sciences and Department of Medicinal Chemistry and Pharmacognosy, University of Illinois at Chicago, 900 S. Ashland, IL 60607, USA.</nlm:affiliation></affiliation></author><author><name sortKey="Ojeda, Isabel" sort="Ojeda, Isabel" uniqKey="Ojeda I" first="Isabel" last="Ojeda">Isabel Ojeda</name><affiliation><nlm:affiliation>Center for Biomolecular Sciences and Department of Medicinal Chemistry and Pharmacognosy, University of Illinois at Chicago, 900 S. Ashland, IL 60607, USA.</nlm:affiliation></affiliation></author><author><name sortKey="Rice, Amy J" sort="Rice, Amy J" uniqKey="Rice A" first="Amy J" last="Rice">Amy J. Rice</name><affiliation><nlm:affiliation>Center for Biomolecular Sciences and Department of Medicinal Chemistry and Pharmacognosy, University of Illinois at Chicago, 900 S. Ashland, IL 60607, USA.</nlm:affiliation></affiliation></author><author><name sortKey="Lv, Haining" sort="Lv, Haining" uniqKey="Lv H" first="Haining" last="Lv">Haining Lv</name><affiliation><nlm:affiliation>Center for Biomolecular Sciences and Department of Medicinal Chemistry and Pharmacognosy, University of Illinois at Chicago, 900 S. Ashland, IL 60607, USA.</nlm:affiliation></affiliation></author><author><name sortKey="Kwon, Youngjin" sort="Kwon, Youngjin" uniqKey="Kwon Y" first="Youngjin" last="Kwon">Youngjin Kwon</name><affiliation><nlm:affiliation>Center for Biomolecular Sciences and Department of Medicinal Chemistry and Pharmacognosy, University of Illinois at Chicago, 900 S. Ashland, IL 60607, USA.</nlm:affiliation></affiliation></author><author><name sortKey="Johnson, Michael E" sort="Johnson, Michael E" uniqKey="Johnson M" first="Michael E" last="Johnson">Michael E. Johnson</name><affiliation><nlm:affiliation>Center for Biomolecular Sciences and Department of Medicinal Chemistry and Pharmacognosy, University of Illinois at Chicago, 900 S. Ashland, IL 60607, USA. Electronic address: mjohnson@uic.edu.</nlm:affiliation></affiliation></author></analytic><series><title level="j">Bioorganic & medicinal chemistry</title><idno type="eISSN">1464-3391</idno><imprint><date when="2019" type="published">2019</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Binding Sites</term><term>Drug Design</term><term>Electron Spin Resonance Spectroscopy</term><term>High-Throughput Screening Assays</term><term>Humans</term><term>Middle East Respiratory Syndrome Coronavirus (enzymology)</term><term>Molecular Docking Simulation</term><term>Peptide Hydrolases (chemistry)</term><term>Peptide Hydrolases (metabolism)</term><term>Protease Inhibitors (chemistry)</term><term>Protease Inhibitors (metabolism)</term><term>Protein Structure, Tertiary</term><term>Small Molecule Libraries (chemistry)</term><term>Small Molecule Libraries (metabolism)</term><term>Structure-Activity Relationship</term><term>Viral Proteins (antagonists & inhibitors)</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="chemistry" xml:lang="en"><term>Peptide Hydrolases</term><term>Protease Inhibitors</term><term>Small Molecule Libraries</term></keywords><keywords scheme="MESH" qualifier="enzymology" xml:lang="en"><term>Middle East Respiratory Syndrome Coronavirus</term></keywords><keywords scheme="MESH" type="chemical" qualifier="metabolism" xml:lang="en"><term>Peptide Hydrolases</term><term>Protease Inhibitors</term><term>Small Molecule Libraries</term><term>Viral Proteins</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Binding Sites</term><term>Drug Design</term><term>Electron Spin Resonance Spectroscopy</term><term>High-Throughput Screening Assays</term><term>Humans</term><term>Molecular Docking Simulation</term><term>Protein Structure, Tertiary</term><term>Structure-Activity Relationship</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">The development of new therapeutic agents against the coronavirus causing Middle East Respiratory Syndrome (MERS) is a continuing imperative. The initial MERS-CoV epidemic was contained entirely through public health measures, but episodic cases continue, as there are currently no therapeutic agents effective in the treatment of MERS-CoV, although multiple strategies have been proposed. In this study, we screened 30,000 compounds from three different compound libraries against one of the essential proteases, the papain-like protease (PL<sup>pro</sup>), using a fluorescence-based enzymatic assay followed by surface plasmon resonance (SPR) direct binding analysis for hit confirmation. Mode of inhibition assays and competition SPR studies revealed two compounds to be competitive inhibitors. To improve upon the inhibitory activity of the best hit compounds, a small fragment library consisting of 352 fragments was screened in the presence of each hit compound, resulting in one fragment that enhanced the IC<sub>50</sub> value of the best hit compound by 3-fold. Molecular docking and MM/PBSA binding energy calculations were used to predict potential binding sites, providing insight for design and synthesis of next-generation compounds.</div></front></TEI><pubmed><MedlineCitation Status="MEDLINE" Owner="NLM"><PMID Version="1">30940566</PMID><DateCompleted><Year>2020</Year><Month>02</Month><Day>20</Day></DateCompleted><DateRevised><Year>2020</Year><Month>04</Month><Day>09</Day></DateRevised><Article PubModel="Print-Electronic"><Journal><ISSN IssnType="Electronic">1464-3391</ISSN><JournalIssue CitedMedium="Internet"><Volume>27</Volume><Issue>10</Issue><PubDate><Year>2019</Year><Month>05</Month><Day>15</Day></PubDate></JournalIssue><Title>Bioorganic & medicinal chemistry</Title><ISOAbbreviation>Bioorg. Med. Chem.</ISOAbbreviation></Journal><ArticleTitle>Identification and design of novel small molecule inhibitors against MERS-CoV papain-like protease via high-throughput screening and molecular modeling.</ArticleTitle><Pagination><MedlinePgn>1981-1989</MedlinePgn></Pagination><ELocationID EIdType="pii" ValidYN="Y">S0968-0896(18)31759-0</ELocationID><ELocationID EIdType="doi" ValidYN="Y">10.1016/j.bmc.2019.03.050</ELocationID><Abstract><AbstractText>The development of new therapeutic agents against the coronavirus causing Middle East Respiratory Syndrome (MERS) is a continuing imperative. The initial MERS-CoV epidemic was contained entirely through public health measures, but episodic cases continue, as there are currently no therapeutic agents effective in the treatment of MERS-CoV, although multiple strategies have been proposed. In this study, we screened 30,000 compounds from three different compound libraries against one of the essential proteases, the papain-like protease (PL<sup>pro</sup>), using a fluorescence-based enzymatic assay followed by surface plasmon resonance (SPR) direct binding analysis for hit confirmation. Mode of inhibition assays and competition SPR studies revealed two compounds to be competitive inhibitors. To improve upon the inhibitory activity of the best hit compounds, a small fragment library consisting of 352 fragments was screened in the presence of each hit compound, resulting in one fragment that enhanced the IC<sub>50</sub> value of the best hit compound by 3-fold. Molecular docking and MM/PBSA binding energy calculations were used to predict potential binding sites, providing insight for design and synthesis of next-generation compounds.</AbstractText><CopyrightInformation>Published by Elsevier Ltd.</CopyrightInformation></Abstract><AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Lee</LastName><ForeName>Hyun</ForeName><Initials>H</Initials><AffiliationInfo><Affiliation>Center for Biomolecular Sciences and Department of Medicinal Chemistry and Pharmacognosy, University of Illinois at Chicago, 900 S. Ashland, IL 60607, USA. Electronic address: danielhl@uic.edu.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Ren</LastName><ForeName>Jinhong</ForeName><Initials>J</Initials><AffiliationInfo><Affiliation>Center for Biomolecular Sciences and Department of Medicinal Chemistry and Pharmacognosy, University of Illinois at Chicago, 900 S. Ashland, IL 60607, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Pesavento</LastName><ForeName>Russell P</ForeName><Initials>RP</Initials><AffiliationInfo><Affiliation>Center for Biomolecular Sciences and Department of Medicinal Chemistry and Pharmacognosy, University of Illinois at Chicago, 900 S. Ashland, IL 60607, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Ojeda</LastName><ForeName>Isabel</ForeName><Initials>I</Initials><AffiliationInfo><Affiliation>Center for Biomolecular Sciences and Department of Medicinal Chemistry and Pharmacognosy, University of Illinois at Chicago, 900 S. Ashland, IL 60607, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Rice</LastName><ForeName>Amy J</ForeName><Initials>AJ</Initials><AffiliationInfo><Affiliation>Center for Biomolecular Sciences and Department of Medicinal Chemistry and Pharmacognosy, University of Illinois at Chicago, 900 S. Ashland, IL 60607, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Lv</LastName><ForeName>Haining</ForeName><Initials>H</Initials><AffiliationInfo><Affiliation>Center for Biomolecular Sciences and Department of Medicinal Chemistry and Pharmacognosy, University of Illinois at Chicago, 900 S. Ashland, IL 60607, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Kwon</LastName><ForeName>Youngjin</ForeName><Initials>Y</Initials><AffiliationInfo><Affiliation>Center for Biomolecular Sciences and Department of Medicinal Chemistry and Pharmacognosy, University of Illinois at Chicago, 900 S. Ashland, IL 60607, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Johnson</LastName><ForeName>Michael E</ForeName><Initials>ME</Initials><AffiliationInfo><Affiliation>Center for Biomolecular Sciences and Department of Medicinal Chemistry and Pharmacognosy, University of Illinois at Chicago, 900 S. Ashland, IL 60607, USA. Electronic address: mjohnson@uic.edu.</Affiliation></AffiliationInfo></Author></AuthorList><Language>eng</Language><GrantList CompleteYN="Y"><Grant><GrantID>P41 GM103311</GrantID><Acronym>GM</Acronym><Agency>NIGMS NIH HHS</Agency><Country>United States</Country></Grant><Grant><GrantID>R56 AI089535</GrantID><Acronym>AI</Acronym><Agency>NIAID 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></PublicationTypeList><ArticleDate DateType="Electronic"><Year>2019</Year><Month>03</Month><Day>26</Day></ArticleDate></Article><MedlineJournalInfo><Country>England</Country><MedlineTA>Bioorg Med Chem</MedlineTA><NlmUniqueID>9413298</NlmUniqueID><ISSNLinking>0968-0896</ISSNLinking></MedlineJournalInfo><ChemicalList><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D011480">Protease Inhibitors</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D054852">Small Molecule Libraries</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D014764">Viral Proteins</NameOfSubstance></Chemical><Chemical><RegistryNumber>EC 3.4.-</RegistryNumber><NameOfSubstance UI="D010447">Peptide Hydrolases</NameOfSubstance></Chemical></ChemicalList><CitationSubset>IM</CitationSubset><MeshHeadingList><MeshHeading><DescriptorName UI="D001665" MajorTopicYN="N">Binding Sites</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D015195" MajorTopicYN="Y">Drug Design</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D004578" MajorTopicYN="N">Electron Spin Resonance Spectroscopy</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D057166" MajorTopicYN="N">High-Throughput Screening Assays</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D006801" MajorTopicYN="N">Humans</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D065207" MajorTopicYN="N">Middle East Respiratory Syndrome Coronavirus</DescriptorName><QualifierName UI="Q000201" MajorTopicYN="Y">enzymology</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D062105" MajorTopicYN="N">Molecular Docking Simulation</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D010447" MajorTopicYN="N">Peptide Hydrolases</DescriptorName><QualifierName UI="Q000737" MajorTopicYN="Y">chemistry</QualifierName><QualifierName UI="Q000378" MajorTopicYN="N">metabolism</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D011480" MajorTopicYN="N">Protease Inhibitors</DescriptorName><QualifierName UI="Q000737" MajorTopicYN="Y">chemistry</QualifierName><QualifierName UI="Q000378" MajorTopicYN="N">metabolism</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D017434" MajorTopicYN="N">Protein Structure, Tertiary</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D054852" MajorTopicYN="N">Small Molecule Libraries</DescriptorName><QualifierName UI="Q000737" MajorTopicYN="Y">chemistry</QualifierName><QualifierName UI="Q000378" MajorTopicYN="N">metabolism</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D013329" MajorTopicYN="N">Structure-Activity Relationship</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D014764" MajorTopicYN="N">Viral Proteins</DescriptorName><QualifierName UI="Q000037" MajorTopicYN="Y">antagonists & inhibitors</QualifierName><QualifierName UI="Q000378" MajorTopicYN="N">metabolism</QualifierName></MeshHeading></MeshHeadingList><KeywordList Owner="NOTNLM"><Keyword MajorTopicYN="Y">Fragment screening</Keyword><Keyword 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PubStatus="entrez"><Year>2019</Year><Month>4</Month><Day>4</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate></History><PublicationStatus>ppublish</PublicationStatus><ArticleIdList><ArticleId IdType="pubmed">30940566</ArticleId><ArticleId IdType="pii">S0968-0896(18)31759-0</ArticleId><ArticleId IdType="doi">10.1016/j.bmc.2019.03.050</ArticleId><ArticleId IdType="pmc">PMC6638567</ArticleId><ArticleId IdType="mid">NIHMS1525927</ArticleId></ArticleIdList><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>Lancet Infect Dis. 2014 Feb;14(2):140-5</Citation><ArticleIdList><ArticleId IdType="pubmed">24355866</ArticleId></ArticleIdList></Reference></ReferenceList><ReferenceList><Reference><Citation>J Biol Chem. 2014 Dec 12;289(50):34667-82</Citation><ArticleIdList><ArticleId IdType="pubmed">25320088</ArticleId></ArticleIdList></Reference></ReferenceList><ReferenceList><Reference><Citation>Nucleic Acids Res. 2011 Jul;39(Web Server issue):W511-7</Citation><ArticleIdList><ArticleId IdType="pubmed">21609950</ArticleId></ArticleIdList></Reference></ReferenceList><ReferenceList><Reference><Citation>J Virol. 2017 Nov 14;91(23):</Citation><ArticleIdList><ArticleId IdType="pubmed">28931677</ArticleId></ArticleIdList></Reference></ReferenceList><ReferenceList><Reference><Citation>Proteins. 2003 Sep 1;52(4):609-23</Citation><ArticleIdList><ArticleId IdType="pubmed">12910460</ArticleId></ArticleIdList></Reference></ReferenceList><ReferenceList><Reference><Citation>Viruses. 2018 Dec 17;10(12):</Citation><ArticleIdList><ArticleId IdType="pubmed">30562987</ArticleId></ArticleIdList></Reference></ReferenceList><ReferenceList><Reference><Citation>J Chem Theory Comput. 2012 Sep 11;8(9):3314-21</Citation><ArticleIdList><ArticleId IdType="pubmed">26605738</ArticleId></ArticleIdList></Reference></ReferenceList><ReferenceList><Reference><Citation>J Virol. 2013 Aug;87(15):8638-50</Citation><ArticleIdList><ArticleId IdType="pubmed">23720729</ArticleId></ArticleIdList></Reference></ReferenceList><ReferenceList><Reference><Citation>Viruses. 2019 Jan 14;11(1):</Citation><ArticleIdList><ArticleId IdType="pubmed">30646569</ArticleId></ArticleIdList></Reference></ReferenceList><ReferenceList><Reference><Citation>J Mol Biol. 2017 Jun 2;429(11):1661-1683</Citation><ArticleIdList><ArticleId IdType="pubmed">28438633</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>Emerg Infect Dis. 2014 Jul;20(7):1260-2</Citation><ArticleIdList><ArticleId IdType="pubmed">24960574</ArticleId></ArticleIdList></Reference></ReferenceList><ReferenceList><Reference><Citation>J Chem Inf Model. 2011 Oct 24;51(10):2778-86</Citation><ArticleIdList><ArticleId IdType="pubmed">21919503</ArticleId></ArticleIdList></Reference></ReferenceList><ReferenceList><Reference><Citation>Antiviral Res. 2014 Sep;109:72-82</Citation><ArticleIdList><ArticleId IdType="pubmed">24992731</ArticleId></ArticleIdList></Reference></ReferenceList><ReferenceList><Reference><Citation>J Comput Chem. 2004 Jul 15;25(9):1157-74</Citation><ArticleIdList><ArticleId IdType="pubmed">15116359</ArticleId></ArticleIdList></Reference></ReferenceList><ReferenceList><Reference><Citation>Clin Microbiol Rev. 2015 Apr;28(2):465-522</Citation><ArticleIdList><ArticleId IdType="pubmed">25810418</ArticleId></ArticleIdList></Reference></ReferenceList><ReferenceList><Reference><Citation>J Comput Chem. 2004 Oct;25(13):1605-12</Citation><ArticleIdList><ArticleId IdType="pubmed">15264254</ArticleId></ArticleIdList></Reference></ReferenceList><ReferenceList><Reference><Citation>Viruses. 2018 Feb 24;10(2):</Citation><ArticleIdList><ArticleId IdType="pubmed">29495250</ArticleId></ArticleIdList></Reference></ReferenceList><ReferenceList><Reference><Citation>Cell Host Microbe. 2014 Sep 10;16(3):328-37</Citation><ArticleIdList><ArticleId IdType="pubmed">25211075</ArticleId></ArticleIdList></Reference></ReferenceList><ReferenceList><Reference><Citation>J Infect Dis. 2015 Dec 15;212(12):1904-13</Citation><ArticleIdList><ArticleId IdType="pubmed">26198719</ArticleId></ArticleIdList></Reference></ReferenceList><ReferenceList><Reference><Citation>Nat Rev Drug Discov. 2016 May;15(5):327-47</Citation><ArticleIdList><ArticleId IdType="pubmed">26868298</ArticleId></ArticleIdList></Reference></ReferenceList><ReferenceList><Reference><Citation>Virology. 2014 Feb;450-451:64-70</Citation><ArticleIdList><ArticleId IdType="pubmed">24503068</ArticleId></ArticleIdList></Reference></ReferenceList><ReferenceList><Reference><Citation>Trials. 2018 Jan 30;19(1):81</Citation><ArticleIdList><ArticleId IdType="pubmed">29382391</ArticleId></ArticleIdList></Reference></ReferenceList><ReferenceList><Reference><Citation>J Virol. 2014 Oct;88(19):11297-303</Citation><ArticleIdList><ArticleId IdType="pubmed">25031349</ArticleId></ArticleIdList></Reference></ReferenceList><ReferenceList><Reference><Citation>ACS Chem Biol. 2015 Jun 19;10(6):1456-65</Citation><ArticleIdList><ArticleId IdType="pubmed">25746232</ArticleId></ArticleIdList></Reference></ReferenceList><ReferenceList><Reference><Citation>Lancet Respir Med. 2015 Jul;3(7):509-10</Citation><ArticleIdList><ArticleId IdType="pubmed">26050550</ArticleId></ArticleIdList></Reference></ReferenceList><ReferenceList><Reference><Citation>Expert Rev Anti Infect Ther. 2017 Mar;15(3):269-275</Citation><ArticleIdList><ArticleId IdType="pubmed">27937060</ArticleId></ArticleIdList></Reference></ReferenceList><ReferenceList><Reference><Citation>Antivir Ther. 2016;21(5):455-9</Citation><ArticleIdList><ArticleId IdType="pubmed">26492219</ArticleId></ArticleIdList></Reference></ReferenceList><ReferenceList><Reference><Citation>Clin Infect Dis. 2014 Nov 1;59(9):1225-33</Citation><ArticleIdList><ArticleId IdType="pubmed">24829216</ArticleId></ArticleIdList></Reference></ReferenceList></PubmedData></pubmed></record>Pour manipuler ce document sous Unix (Dilib)
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HfdIndexSelect -h $EXPLOR_AREA/Data/PubMed/Corpus/RBID.i -Sk "pubmed:30940566" \
| HfdSelect -Kh $EXPLOR_AREA/Data/PubMed/Corpus/biblio.hfd \
| NlmPubMed2Wicri -a MersV1
| This area was generated with Dilib version V0.6.33. |  |