Inhibitor recognition specificity of MERS-CoV papain-like protease may differ from that of SARS-CoV.
Identifieur interne : 000E47 ( PubMed/Corpus ); précédent : 000E46; suivant : 000E48Inhibitor recognition specificity of MERS-CoV papain-like protease may differ from that of SARS-CoV.
Auteurs : Hyun Lee ; Hao Lei ; Bernard D. Santarsiero ; Joseph L. Gatuz ; Shuyi Cao ; Amy J. Rice ; Kavankumar Patel ; Michael Z. Szypulinski ; Isabel Ojeda ; Arun K. Ghosh ; Michael E. JohnsonSource :
- ACS chemical biology [ 1554-8937 ] ; 2015.
English descriptors
- KwdEn :
- Allosteric Regulation, Amino Acid Sequence, Antiviral Agents (chemistry), Catalytic Domain, Cysteine Endopeptidases (chemistry), Endopeptidases (chemistry), High-Throughput Screening Assays, Humans, Kinetics, Middle East Respiratory Syndrome Coronavirus (chemistry), Middle East Respiratory Syndrome Coronavirus (enzymology), Models, Molecular, Molecular Sequence Data, Protease Inhibitors (chemistry), Protein Binding, Protein Structure, Secondary, Recombinant Proteins (chemistry), SARS Virus (chemistry), SARS Virus (enzymology), Species Specificity, Surface Plasmon Resonance, Ubiquitin Thiolesterase (antagonists & inhibitors), Ubiquitin Thiolesterase (chemistry), Viral Proteins (antagonists & inhibitors), Viral Proteins (chemistry).
- MESH :
- chemical , antagonists & inhibitors : Ubiquitin Thiolesterase, Viral Proteins.
- chemical , chemistry : Antiviral Agents, Cysteine Endopeptidases, Endopeptidases, Protease Inhibitors, Recombinant Proteins, Ubiquitin Thiolesterase, Viral Proteins.
- chemistry : Middle East Respiratory Syndrome Coronavirus, SARS Virus.
- enzymology : Middle East Respiratory Syndrome Coronavirus, SARS Virus.
- Allosteric Regulation, Amino Acid Sequence, Catalytic Domain, High-Throughput Screening Assays, Humans, Kinetics, Models, Molecular, Molecular Sequence Data, Protein Binding, Protein Structure, Secondary, Species Specificity, Surface Plasmon Resonance.
Abstract
The Middle East Respiratory Syndrome coronavirus (MERS-CoV) papain-like protease (PLpro) blocking loop 2 (BL2) structure differs significantly from that of SARS-CoV PLpro, where it has been proven to play a crucial role in SARS-CoV PLpro inhibitor binding. Four SARS-CoV PLpro lead inhibitors were tested against MERS-CoV PLpro, none of which were effective against MERS-CoV PLpro. Structure and sequence alignments revealed that two residues, Y269 and Q270, responsible for inhibitor binding to SARS-CoV PLpro, were replaced by T274 and A275 in MERS-CoV PLpro, making critical binding interactions difficult to form for similar types of inhibitors. High-throughput screening (HTS) of 25 000 compounds against both PLpro enzymes identified a small fragment-like noncovalent dual inhibitor. Mode of inhibition studies by enzyme kinetics and competition surface plasmon resonance (SPR) analyses suggested that this compound acts as a competitive inhibitor with an IC50 of 6 μM against MERS-CoV PLpro, indicating that it binds to the active site, whereas it acts as an allosteric inhibitor against SARS-CoV PLpro with an IC50 of 11 μM. These results raised the possibility that inhibitor recognition specificity of MERS-CoV PLpro may differ from that of SARS-CoV PLpro. In addition, inhibitory activity of this compound was selective for SARS-CoV and MERS-CoV PLpro enzymes over two human homologues, the ubiquitin C-terminal hydrolases 1 and 3 (hUCH-L1 and hUCH-L3).
DOI: 10.1021/cb500917m
PubMed: 25746232
Links to Exploration step
pubmed:25746232Le document en format XML
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Ashland, Chicago, Illinois 60607, United States.</nlm:affiliation></affiliation></author><author><name sortKey="Lei, Hao" sort="Lei, Hao" uniqKey="Lei H" first="Hao" last="Lei">Hao Lei</name><affiliation><nlm:affiliation>†Center for Pharmaceutical Biotechnology and Department of Medicinal Chemistry and Pharmacognosy, University of Illinois at Chicago, 900 S. Ashland, Chicago, Illinois 60607, United States.</nlm:affiliation></affiliation></author><author><name sortKey="Santarsiero, Bernard D" sort="Santarsiero, Bernard D" uniqKey="Santarsiero B" first="Bernard D" last="Santarsiero">Bernard D. Santarsiero</name><affiliation><nlm:affiliation>†Center for Pharmaceutical Biotechnology and Department of Medicinal Chemistry and Pharmacognosy, University of Illinois at Chicago, 900 S. Ashland, Chicago, Illinois 60607, United States.</nlm:affiliation></affiliation></author><author><name sortKey="Gatuz, Joseph L" sort="Gatuz, Joseph L" uniqKey="Gatuz J" first="Joseph L" last="Gatuz">Joseph L. Gatuz</name><affiliation><nlm:affiliation>†Center for Pharmaceutical Biotechnology and Department of Medicinal Chemistry and Pharmacognosy, University of Illinois at Chicago, 900 S. Ashland, Chicago, Illinois 60607, United States.</nlm:affiliation></affiliation></author><author><name sortKey="Cao, Shuyi" sort="Cao, Shuyi" uniqKey="Cao S" first="Shuyi" last="Cao">Shuyi Cao</name><affiliation><nlm:affiliation>†Center for Pharmaceutical Biotechnology and Department of Medicinal Chemistry and Pharmacognosy, University of Illinois at Chicago, 900 S. Ashland, Chicago, Illinois 60607, United States.</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 Pharmaceutical Biotechnology and Department of Medicinal Chemistry and Pharmacognosy, University of Illinois at Chicago, 900 S. Ashland, Chicago, Illinois 60607, United States.</nlm:affiliation></affiliation></author><author><name sortKey="Patel, Kavankumar" sort="Patel, Kavankumar" uniqKey="Patel K" first="Kavankumar" last="Patel">Kavankumar Patel</name><affiliation><nlm:affiliation>†Center for Pharmaceutical Biotechnology and Department of Medicinal Chemistry and Pharmacognosy, University of Illinois at Chicago, 900 S. Ashland, Chicago, Illinois 60607, United States.</nlm:affiliation></affiliation></author><author><name sortKey="Szypulinski, Michael Z" sort="Szypulinski, Michael Z" uniqKey="Szypulinski M" first="Michael Z" last="Szypulinski">Michael Z. Szypulinski</name><affiliation><nlm:affiliation>†Center for Pharmaceutical Biotechnology and Department of Medicinal Chemistry and Pharmacognosy, University of Illinois at Chicago, 900 S. Ashland, Chicago, Illinois 60607, United States.</nlm:affiliation></affiliation></author><author><name sortKey="Ojeda, Isabel" sort="Ojeda, Isabel" uniqKey="Ojeda I" first="Isabel" last="Ojeda">Isabel Ojeda</name></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>‡Departments of Chemistry and Medicinal Chemistry, Purdue University, 560 Oval Drive, West Lafayette, Indiana 47907, United States.</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 Pharmaceutical Biotechnology and Department of Medicinal Chemistry and Pharmacognosy, University of Illinois at Chicago, 900 S. Ashland, Chicago, Illinois 60607, United States.</nlm:affiliation></affiliation></author></analytic><series><title level="j">ACS chemical biology</title><idno type="eISSN">1554-8937</idno><imprint><date when="2015" type="published">2015</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Allosteric Regulation</term><term>Amino Acid Sequence</term><term>Antiviral Agents (chemistry)</term><term>Catalytic Domain</term><term>Cysteine Endopeptidases (chemistry)</term><term>Endopeptidases (chemistry)</term><term>High-Throughput Screening Assays</term><term>Humans</term><term>Kinetics</term><term>Middle East Respiratory Syndrome Coronavirus (chemistry)</term><term>Middle East Respiratory Syndrome Coronavirus (enzymology)</term><term>Models, Molecular</term><term>Molecular Sequence Data</term><term>Protease Inhibitors (chemistry)</term><term>Protein Binding</term><term>Protein Structure, Secondary</term><term>Recombinant Proteins (chemistry)</term><term>SARS Virus (chemistry)</term><term>SARS Virus (enzymology)</term><term>Species Specificity</term><term>Surface Plasmon Resonance</term><term>Ubiquitin Thiolesterase (antagonists & inhibitors)</term><term>Ubiquitin Thiolesterase (chemistry)</term><term>Viral Proteins (antagonists & inhibitors)</term><term>Viral Proteins (chemistry)</term></keywords><keywords scheme="MESH" type="chemical" qualifier="antagonists & inhibitors" xml:lang="en"><term>Ubiquitin Thiolesterase</term><term>Viral Proteins</term></keywords><keywords scheme="MESH" type="chemical" qualifier="chemistry" xml:lang="en"><term>Antiviral Agents</term><term>Cysteine Endopeptidases</term><term>Endopeptidases</term><term>Protease Inhibitors</term><term>Recombinant Proteins</term><term>Ubiquitin Thiolesterase</term><term>Viral Proteins</term></keywords><keywords scheme="MESH" qualifier="chemistry" xml:lang="en"><term>Middle East Respiratory Syndrome Coronavirus</term><term>SARS Virus</term></keywords><keywords scheme="MESH" qualifier="enzymology" xml:lang="en"><term>Middle East Respiratory Syndrome Coronavirus</term><term>SARS Virus</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Allosteric Regulation</term><term>Amino Acid Sequence</term><term>Catalytic Domain</term><term>High-Throughput Screening Assays</term><term>Humans</term><term>Kinetics</term><term>Models, Molecular</term><term>Molecular Sequence Data</term><term>Protein Binding</term><term>Protein Structure, Secondary</term><term>Species Specificity</term><term>Surface Plasmon Resonance</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">The Middle East Respiratory Syndrome coronavirus (MERS-CoV) papain-like protease (PLpro) blocking loop 2 (BL2) structure differs significantly from that of SARS-CoV PLpro, where it has been proven to play a crucial role in SARS-CoV PLpro inhibitor binding. Four SARS-CoV PLpro lead inhibitors were tested against MERS-CoV PLpro, none of which were effective against MERS-CoV PLpro. Structure and sequence alignments revealed that two residues, Y269 and Q270, responsible for inhibitor binding to SARS-CoV PLpro, were replaced by T274 and A275 in MERS-CoV PLpro, making critical binding interactions difficult to form for similar types of inhibitors. High-throughput screening (HTS) of 25 000 compounds against both PLpro enzymes identified a small fragment-like noncovalent dual inhibitor. Mode of inhibition studies by enzyme kinetics and competition surface plasmon resonance (SPR) analyses suggested that this compound acts as a competitive inhibitor with an IC50 of 6 μM against MERS-CoV PLpro, indicating that it binds to the active site, whereas it acts as an allosteric inhibitor against SARS-CoV PLpro with an IC50 of 11 μM. These results raised the possibility that inhibitor recognition specificity of MERS-CoV PLpro may differ from that of SARS-CoV PLpro. In addition, inhibitory activity of this compound was selective for SARS-CoV and MERS-CoV PLpro enzymes over two human homologues, the ubiquitin C-terminal hydrolases 1 and 3 (hUCH-L1 and hUCH-L3). </div></front></TEI><pubmed><MedlineCitation Status="MEDLINE" Owner="NLM"><PMID Version="1">25746232</PMID><DateCompleted><Year>2016</Year><Month>03</Month><Day>10</Day></DateCompleted><DateRevised><Year>2020</Year><Month>03</Month><Day>25</Day></DateRevised><Article PubModel="Print-Electronic"><Journal><ISSN IssnType="Electronic">1554-8937</ISSN><JournalIssue CitedMedium="Internet"><Volume>10</Volume><Issue>6</Issue><PubDate><Year>2015</Year><Month>Jun</Month><Day>19</Day></PubDate></JournalIssue><Title>ACS chemical biology</Title><ISOAbbreviation>ACS Chem. Biol.</ISOAbbreviation></Journal><ArticleTitle>Inhibitor recognition specificity of MERS-CoV papain-like protease may differ from that of SARS-CoV.</ArticleTitle><Pagination><MedlinePgn>1456-65</MedlinePgn></Pagination><ELocationID EIdType="doi" ValidYN="Y">10.1021/cb500917m</ELocationID><Abstract><AbstractText>The Middle East Respiratory Syndrome coronavirus (MERS-CoV) papain-like protease (PLpro) blocking loop 2 (BL2) structure differs significantly from that of SARS-CoV PLpro, where it has been proven to play a crucial role in SARS-CoV PLpro inhibitor binding. Four SARS-CoV PLpro lead inhibitors were tested against MERS-CoV PLpro, none of which were effective against MERS-CoV PLpro. Structure and sequence alignments revealed that two residues, Y269 and Q270, responsible for inhibitor binding to SARS-CoV PLpro, were replaced by T274 and A275 in MERS-CoV PLpro, making critical binding interactions difficult to form for similar types of inhibitors. High-throughput screening (HTS) of 25 000 compounds against both PLpro enzymes identified a small fragment-like noncovalent dual inhibitor. Mode of inhibition studies by enzyme kinetics and competition surface plasmon resonance (SPR) analyses suggested that this compound acts as a competitive inhibitor with an IC50 of 6 μM against MERS-CoV PLpro, indicating that it binds to the active site, whereas it acts as an allosteric inhibitor against SARS-CoV PLpro with an IC50 of 11 μM. These results raised the possibility that inhibitor recognition specificity of MERS-CoV PLpro may differ from that of SARS-CoV PLpro. In addition, inhibitory activity of this compound was selective for SARS-CoV and MERS-CoV PLpro enzymes over two human homologues, the ubiquitin C-terminal hydrolases 1 and 3 (hUCH-L1 and hUCH-L3). </AbstractText></Abstract><AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Lee</LastName><ForeName>Hyun</ForeName><Initials>H</Initials><AffiliationInfo><Affiliation>†Center for Pharmaceutical Biotechnology and Department of Medicinal Chemistry and Pharmacognosy, University of Illinois at Chicago, 900 S. Ashland, Chicago, Illinois 60607, United States.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Lei</LastName><ForeName>Hao</ForeName><Initials>H</Initials><AffiliationInfo><Affiliation>†Center for Pharmaceutical Biotechnology and Department of Medicinal Chemistry and Pharmacognosy, University of Illinois at Chicago, 900 S. Ashland, Chicago, Illinois 60607, United States.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Santarsiero</LastName><ForeName>Bernard D</ForeName><Initials>BD</Initials><AffiliationInfo><Affiliation>†Center for Pharmaceutical Biotechnology and Department of Medicinal Chemistry and Pharmacognosy, University of Illinois at Chicago, 900 S. Ashland, Chicago, Illinois 60607, United States.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Gatuz</LastName><ForeName>Joseph L</ForeName><Initials>JL</Initials><AffiliationInfo><Affiliation>†Center for Pharmaceutical Biotechnology and Department of Medicinal Chemistry and Pharmacognosy, University of Illinois at Chicago, 900 S. Ashland, Chicago, Illinois 60607, United States.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Cao</LastName><ForeName>Shuyi</ForeName><Initials>S</Initials><AffiliationInfo><Affiliation>†Center for Pharmaceutical Biotechnology and Department of Medicinal Chemistry and Pharmacognosy, University of Illinois at Chicago, 900 S. Ashland, Chicago, Illinois 60607, United States.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Rice</LastName><ForeName>Amy J</ForeName><Initials>AJ</Initials><AffiliationInfo><Affiliation>†Center for Pharmaceutical Biotechnology and Department of Medicinal Chemistry and Pharmacognosy, University of Illinois at Chicago, 900 S. Ashland, Chicago, Illinois 60607, United States.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Patel</LastName><ForeName>Kavankumar</ForeName><Initials>K</Initials><AffiliationInfo><Affiliation>†Center for Pharmaceutical Biotechnology and Department of Medicinal Chemistry and Pharmacognosy, University of Illinois at Chicago, 900 S. Ashland, Chicago, Illinois 60607, United States.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Szypulinski</LastName><ForeName>Michael Z</ForeName><Initials>MZ</Initials><AffiliationInfo><Affiliation>†Center for Pharmaceutical Biotechnology and Department of Medicinal Chemistry and Pharmacognosy, University of Illinois at Chicago, 900 S. Ashland, Chicago, Illinois 60607, United States.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Ojeda</LastName><ForeName>Isabel</ForeName><Initials>I</Initials></Author><Author ValidYN="Y"><LastName>Ghosh</LastName><ForeName>Arun K</ForeName><Initials>AK</Initials><AffiliationInfo><Affiliation>‡Departments of Chemistry and Medicinal Chemistry, Purdue University, 560 Oval Drive, West Lafayette, Indiana 47907, United States.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Johnson</LastName><ForeName>Michael E</ForeName><Initials>ME</Initials><AffiliationInfo><Affiliation>†Center for Pharmaceutical Biotechnology and Department of Medicinal Chemistry and Pharmacognosy, University of Illinois at Chicago, 900 S. Ashland, Chicago, Illinois 60607, United States.</Affiliation></AffiliationInfo></Author></AuthorList><Language>eng</Language><GrantList CompleteYN="Y"><Grant><GrantID>R37 GM053386</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><Grant><GrantID>T32 DE018381</GrantID><Acronym>DE</Acronym><Agency>NIDCR NIH HHS</Agency><Country>United States</Country></Grant><Grant><GrantID>T32-DE018381</GrantID><Acronym>DE</Acronym><Agency>NIDCR 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="D013486">Research Support, U.S. Gov't, Non-P.H.S.</PublicationType></PublicationTypeList><ArticleDate DateType="Electronic"><Year>2015</Year><Month>03</Month><Day>16</Day></ArticleDate></Article><MedlineJournalInfo><Country>United States</Country><MedlineTA>ACS Chem Biol</MedlineTA><NlmUniqueID>101282906</NlmUniqueID><ISSNLinking>1554-8929</ISSNLinking></MedlineJournalInfo><ChemicalList><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D000998">Antiviral Agents</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D011480">Protease Inhibitors</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D011994">Recombinant Proteins</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="C482860">UCHL1 protein, human</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D014764">Viral Proteins</NameOfSubstance></Chemical><Chemical><RegistryNumber>EC 3.4.-</RegistryNumber><NameOfSubstance UI="D010450">Endopeptidases</NameOfSubstance></Chemical><Chemical><RegistryNumber>EC 3.4.19.12</RegistryNumber><NameOfSubstance UI="C509806">UCHL3 protein, human</NameOfSubstance></Chemical><Chemical><RegistryNumber>EC 3.4.19.12</RegistryNumber><NameOfSubstance UI="D043222">Ubiquitin Thiolesterase</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="D000494" MajorTopicYN="N">Allosteric Regulation</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D000595" MajorTopicYN="N">Amino Acid Sequence</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D000998" MajorTopicYN="N">Antiviral Agents</DescriptorName><QualifierName UI="Q000737" MajorTopicYN="Y">chemistry</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D020134" MajorTopicYN="N">Catalytic Domain</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D003546" MajorTopicYN="N">Cysteine Endopeptidases</DescriptorName><QualifierName UI="Q000737" MajorTopicYN="N">chemistry</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D010450" MajorTopicYN="N">Endopeptidases</DescriptorName><QualifierName UI="Q000737" MajorTopicYN="N">chemistry</QualifierName></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="D007700" MajorTopicYN="N">Kinetics</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D065207" MajorTopicYN="N">Middle East Respiratory Syndrome Coronavirus</DescriptorName><QualifierName UI="Q000737" MajorTopicYN="Y">chemistry</QualifierName><QualifierName UI="Q000201" MajorTopicYN="N">enzymology</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D008958" MajorTopicYN="N">Models, Molecular</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D008969" MajorTopicYN="N">Molecular Sequence Data</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D011480" MajorTopicYN="N">Protease Inhibitors</DescriptorName><QualifierName UI="Q000737" MajorTopicYN="Y">chemistry</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D011485" MajorTopicYN="N">Protein Binding</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D017433" MajorTopicYN="N">Protein Structure, Secondary</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D011994" MajorTopicYN="N">Recombinant Proteins</DescriptorName><QualifierName UI="Q000737" MajorTopicYN="N">chemistry</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D045473" MajorTopicYN="N">SARS 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