MersV1, PubMed, Checkpoint, bibRecord, 001065

Identification of Nafamostat as a Potent Inhibitor of Middle East Respiratory Syndrome Coronavirus S Protein-Mediated Membrane Fusion Using the Split-Protein-Based Cell-Cell Fusion Assay.

Identifieur interne : 001065 ( PubMed/Checkpoint ); précédent : 001064; suivant : 001066

Identification of Nafamostat as a Potent Inhibitor of Middle East Respiratory Syndrome Coronavirus S Protein-Mediated Membrane Fusion Using the Split-Protein-Based Cell-Cell Fusion Assay.

Auteurs : Mizuki Yamamoto [Japon] ; Shutoku Matsuyama [Japon] ; Xiao Li [République populaire de Chine] ; Makoto Takeda [Japon] ; Yasushi Kawaguchi [Japon] ; Jun-Ichiro Inoue [Japon] ; Zene Matsuda [Japon]

Source :

Antimicrobial agents and chemotherapy [ 1098-6596 ] ; 2016.

RBID : pubmed:27550352

Descripteurs français

English descriptors

KwdEn :
- Cathepsins (genetics), Cathepsins (metabolism), Cell Fusion, Cell Membrane (drug effects), Cell Membrane (metabolism), Cell Membrane (virology), Dipeptidyl Peptidase 4 (genetics), Dipeptidyl Peptidase 4 (metabolism), Furin (genetics), Furin (metabolism), Gene Expression Regulation, Genes, Reporter, Guanidines (pharmacology), HEK293 Cells, High-Throughput Screening Assays, Host-Pathogen Interactions, Humans, Intracellular Membranes (drug effects), Intracellular Membranes (metabolism), Intracellular Membranes (virology), Luciferases (genetics), Luciferases (metabolism), Membrane Fusion (drug effects), Middle East Respiratory Syndrome Coronavirus (drug effects), Middle East Respiratory Syndrome Coronavirus (genetics), Middle East Respiratory Syndrome Coronavirus (growth & development), Proteolysis, Serine Endopeptidases (genetics), Serine Endopeptidases (metabolism), Spike Glycoprotein, Coronavirus (antagonists & inhibitors), Spike Glycoprotein, Coronavirus (genetics), Spike Glycoprotein, Coronavirus (metabolism), Viral Fusion Protein Inhibitors (pharmacology).
MESH :
- chemical , antagonists & inhibitors : Spike Glycoprotein, Coronavirus.
- chemical , genetics : Cathepsins, Dipeptidyl Peptidase 4, Furin, Luciferases, Serine Endopeptidases, Spike Glycoprotein, Coronavirus.
- chemical , metabolism : Cathepsins, Dipeptidyl Peptidase 4, Furin, Luciferases, Serine Endopeptidases, Spike Glycoprotein, Coronavirus.
- drug effects : Cell Membrane, Intracellular Membranes, Membrane Fusion, Middle East Respiratory Syndrome Coronavirus.
- genetics : Middle East Respiratory Syndrome Coronavirus.
- growth & development : Middle East Respiratory Syndrome Coronavirus.
- metabolism : Cell Membrane, Intracellular Membranes.
- chemical , pharmacology : Guanidines, Viral Fusion Protein Inhibitors.
- virology : Cell Membrane, Intracellular Membranes.
- Cell Fusion, Gene Expression Regulation, Genes, Reporter, HEK293 Cells, High-Throughput Screening Assays, Host-Pathogen Interactions, Humans, Proteolysis.

Abstract

Middle East respiratory syndrome (MERS) is an emerging infectious disease associated with a relatively high mortality rate of approximately 40%. MERS is caused by MERS coronavirus (MERS-CoV) infection, and no specific drugs or vaccines are currently available to prevent MERS-CoV infection. MERS-CoV is an enveloped virus, and its envelope protein (S protein) mediates membrane fusion at the plasma membrane or endosomal membrane. Multiple proteolysis by host proteases, such as furin, transmembrane protease serine 2 (TMPRSS2), and cathepsins, causes the S protein to become fusion competent. TMPRSS2, which is localized to the plasma membrane, is a serine protease responsible for the proteolysis of S in the post-receptor-binding stage. Here, we developed a cell-based fusion assay for S in a TMPRSS2-dependent manner using cell lines expressing Renilla luciferase (RL)-based split reporter proteins. S was stably expressed in the effector cells, and the corresponding receptor for S, CD26, was stably coexpressed with TMPRSS2 in the target cells. Membrane fusion between these effector and target cells was quantitatively measured by determining the RL activity. The assay was optimized for a 384-well format, and nafamostat, a serine protease inhibitor, was identified as a potent inhibitor of S-mediated membrane fusion in a screening of about 1,000 drugs approved for use by the U.S. Food and Drug Administration. Nafamostat also blocked MERS-CoV infection in vitro Our assay has the potential to facilitate the discovery of new inhibitors of membrane fusion of MERS-CoV as well as other viruses that rely on the activity of TMPRSS2.

DOI: 10.1128/AAC.01043-16
PubMed: 27550352

Affiliations:

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<term>Cathepsins (metabolism)</term>
<term>Cell Fusion</term>
<term>Cell Membrane (drug effects)</term>
<term>Cell Membrane (metabolism)</term>
<term>Cell Membrane (virology)</term>
<term>Dipeptidyl Peptidase 4 (genetics)</term>
<term>Dipeptidyl Peptidase 4 (metabolism)</term>
<term>Furin (genetics)</term>
<term>Furin (metabolism)</term>
<term>Gene Expression Regulation</term>
<term>Genes, Reporter</term>
<term>Guanidines (pharmacology)</term>
<term>HEK293 Cells</term>
<term>High-Throughput Screening Assays</term>
<term>Host-Pathogen Interactions</term>
<term>Humans</term>
<term>Intracellular Membranes (drug effects)</term>
<term>Intracellular Membranes (metabolism)</term>
<term>Intracellular Membranes (virology)</term>
<term>Luciferases (genetics)</term>
<term>Luciferases (metabolism)</term>
<term>Membrane Fusion (drug effects)</term>
<term>Middle East Respiratory Syndrome Coronavirus (drug effects)</term>
<term>Middle East Respiratory Syndrome Coronavirus (genetics)</term>
<term>Middle East Respiratory Syndrome Coronavirus (growth & development)</term>
<term>Proteolysis</term>
<term>Serine Endopeptidases (genetics)</term>
<term>Serine Endopeptidases (metabolism)</term>
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<term>Cathepsines (métabolisme)</term>
<term>Cellules HEK293</term>
<term>Coronavirus du syndrome respiratoire du Moyen-Orient ()</term>
<term>Coronavirus du syndrome respiratoire du Moyen-Orient (croissance et développement)</term>
<term>Coronavirus du syndrome respiratoire du Moyen-Orient (génétique)</term>
<term>Dipeptidyl peptidase 4 (génétique)</term>
<term>Dipeptidyl peptidase 4 (métabolisme)</term>
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<term>Furine (métabolisme)</term>
<term>Fusion cellulaire</term>
<term>Fusion membranaire ()</term>
<term>Glycoprotéine de spicule des coronavirus (antagonistes et inhibiteurs)</term>
<term>Glycoprotéine de spicule des coronavirus (génétique)</term>
<term>Glycoprotéine de spicule des coronavirus (métabolisme)</term>
<term>Guanidines (pharmacologie)</term>
<term>Gènes rapporteurs</term>
<term>Humains</term>
<term>Inhibiteurs des protéines de fusion virale (pharmacologie)</term>
<term>Interactions hôte-pathogène</term>
<term>Luciferases (génétique)</term>
<term>Luciferases (métabolisme)</term>
<term>Membrane cellulaire ()</term>
<term>Membrane cellulaire (métabolisme)</term>
<term>Membrane cellulaire (virologie)</term>
<term>Membranes intracellulaires ()</term>
<term>Membranes intracellulaires (métabolisme)</term>
<term>Membranes intracellulaires (virologie)</term>
<term>Protéolyse</term>
<term>Régulation de l'expression des gènes</term>
<term>Serine endopeptidases (génétique)</term>
<term>Serine endopeptidases (métabolisme)</term>
<term>Tests de criblage à haut débit</term>
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<term>Furin</term>
<term>Luciferases</term>
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<term>Dipeptidyl Peptidase 4</term>
<term>Furin</term>
<term>Luciferases</term>
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<term>Coronavirus du syndrome respiratoire du Moyen-Orient</term>
<term>Dipeptidyl peptidase 4</term>
<term>Furine</term>
<term>Glycoprotéine de spicule des coronavirus</term>
<term>Luciferases</term>
<term>Serine endopeptidases</term>
</keywords>
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<term>Intracellular Membranes</term>
</keywords>
<keywords scheme="MESH" qualifier="métabolisme" xml:lang="fr"><term>Cathepsines</term>
<term>Dipeptidyl peptidase 4</term>
<term>Furine</term>
<term>Glycoprotéine de spicule des coronavirus</term>
<term>Luciferases</term>
<term>Membrane cellulaire</term>
<term>Membranes intracellulaires</term>
<term>Serine endopeptidases</term>
</keywords>
<keywords scheme="MESH" qualifier="pharmacologie" xml:lang="fr"><term>Guanidines</term>
<term>Inhibiteurs des protéines de fusion virale</term>
</keywords>
<keywords scheme="MESH" type="chemical" qualifier="pharmacology" xml:lang="en"><term>Guanidines</term>
<term>Viral Fusion Protein Inhibitors</term>
</keywords>
<keywords scheme="MESH" qualifier="virologie" xml:lang="fr"><term>Membrane cellulaire</term>
<term>Membranes intracellulaires</term>
</keywords>
<keywords scheme="MESH" qualifier="virology" xml:lang="en"><term>Cell Membrane</term>
<term>Intracellular Membranes</term>
</keywords>
<keywords scheme="MESH" xml:lang="en"><term>Cell Fusion</term>
<term>Gene Expression Regulation</term>
<term>Genes, Reporter</term>
<term>HEK293 Cells</term>
<term>High-Throughput Screening Assays</term>
<term>Host-Pathogen Interactions</term>
<term>Humans</term>
<term>Proteolysis</term>
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<term>Coronavirus du syndrome respiratoire du Moyen-Orient</term>
<term>Fusion cellulaire</term>
<term>Fusion membranaire</term>
<term>Gènes rapporteurs</term>
<term>Humains</term>
<term>Interactions hôte-pathogène</term>
<term>Membrane cellulaire</term>
<term>Membranes intracellulaires</term>
<term>Protéolyse</term>
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<front><div type="abstract" xml:lang="en">Middle East respiratory syndrome (MERS) is an emerging infectious disease associated with a relatively high mortality rate of approximately 40%. MERS is caused by MERS coronavirus (MERS-CoV) infection, and no specific drugs or vaccines are currently available to prevent MERS-CoV infection. MERS-CoV is an enveloped virus, and its envelope protein (S protein) mediates membrane fusion at the plasma membrane or endosomal membrane. Multiple proteolysis by host proteases, such as furin, transmembrane protease serine 2 (TMPRSS2), and cathepsins, causes the S protein to become fusion competent. TMPRSS2, which is localized to the plasma membrane, is a serine protease responsible for the proteolysis of S in the post-receptor-binding stage. Here, we developed a cell-based fusion assay for S in a TMPRSS2-dependent manner using cell lines expressing Renilla luciferase (RL)-based split reporter proteins. S was stably expressed in the effector cells, and the corresponding receptor for S, CD26, was stably coexpressed with TMPRSS2 in the target cells. Membrane fusion between these effector and target cells was quantitatively measured by determining the RL activity. The assay was optimized for a 384-well format, and nafamostat, a serine protease inhibitor, was identified as a potent inhibitor of S-mediated membrane fusion in a screening of about 1,000 drugs approved for use by the U.S. Food and Drug Administration. Nafamostat also blocked MERS-CoV infection in vitro Our assay has the potential to facilitate the discovery of new inhibitors of membrane fusion of MERS-CoV as well as other viruses that rely on the activity of TMPRSS2.</div>
</front>
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<Month>08</Month>
<Day>17</Day>
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<DateRevised><Year>2018</Year>
<Month>11</Month>
<Day>13</Day>
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<Issue>11</Issue>
<PubDate><Year>2016</Year>
<Month>11</Month>
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<Title>Antimicrobial agents and chemotherapy</Title>
<ISOAbbreviation>Antimicrob. Agents Chemother.</ISOAbbreviation>
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<ArticleTitle>Identification of Nafamostat as a Potent Inhibitor of Middle East Respiratory Syndrome Coronavirus S Protein-Mediated Membrane Fusion Using the Split-Protein-Based Cell-Cell Fusion Assay.</ArticleTitle>
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<ELocationID EIdType="doi" ValidYN="Y">10.1128/AAC.01043-16</ELocationID>
<Abstract><AbstractText>Middle East respiratory syndrome (MERS) is an emerging infectious disease associated with a relatively high mortality rate of approximately 40%. MERS is caused by MERS coronavirus (MERS-CoV) infection, and no specific drugs or vaccines are currently available to prevent MERS-CoV infection. MERS-CoV is an enveloped virus, and its envelope protein (S protein) mediates membrane fusion at the plasma membrane or endosomal membrane. Multiple proteolysis by host proteases, such as furin, transmembrane protease serine 2 (TMPRSS2), and cathepsins, causes the S protein to become fusion competent. TMPRSS2, which is localized to the plasma membrane, is a serine protease responsible for the proteolysis of S in the post-receptor-binding stage. Here, we developed a cell-based fusion assay for S in a TMPRSS2-dependent manner using cell lines expressing Renilla luciferase (RL)-based split reporter proteins. S was stably expressed in the effector cells, and the corresponding receptor for S, CD26, was stably coexpressed with TMPRSS2 in the target cells. Membrane fusion between these effector and target cells was quantitatively measured by determining the RL activity. The assay was optimized for a 384-well format, and nafamostat, a serine protease inhibitor, was identified as a potent inhibitor of S-mediated membrane fusion in a screening of about 1,000 drugs approved for use by the U.S. Food and Drug Administration. Nafamostat also blocked MERS-CoV infection in vitro Our assay has the potential to facilitate the discovery of new inhibitors of membrane fusion of MERS-CoV as well as other viruses that rely on the activity of TMPRSS2.</AbstractText>
<CopyrightInformation>Copyright © 2016, American Society for Microbiology. All Rights Reserved.</CopyrightInformation>
</Abstract>
<AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Yamamoto</LastName>
<ForeName>Mizuki</ForeName>
<Initials>M</Initials>
<AffiliationInfo><Affiliation>Research Center for Asian Infectious Diseases, Institute of Medical Science, The University of Tokyo, Tokyo, Japan.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Matsuyama</LastName>
<ForeName>Shutoku</ForeName>
<Initials>S</Initials>
<AffiliationInfo><Affiliation>Department of Virology III, National Institute of Infectious Diseases, Tokyo, Japan.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Li</LastName>
<ForeName>Xiao</ForeName>
<Initials>X</Initials>
<AffiliationInfo><Affiliation>Laboratory of Structural Virology and Immunology, Institute of Biophysics, Chinese Academy of Sciences, Beijing, People's Republic of China.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Takeda</LastName>
<ForeName>Makoto</ForeName>
<Initials>M</Initials>
<AffiliationInfo><Affiliation>Department of Virology III, National Institute of Infectious Diseases, Tokyo, Japan.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Kawaguchi</LastName>
<ForeName>Yasushi</ForeName>
<Initials>Y</Initials>
<AffiliationInfo><Affiliation>Research Center for Asian Infectious Diseases, Institute of Medical Science, The University of Tokyo, Tokyo, Japan.</Affiliation>
</AffiliationInfo>
<AffiliationInfo><Affiliation>Division of Molecular Virology, Department of Microbiology and Immunology, Institute of Medical Science, The University of Tokyo, Tokyo, Japan.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Inoue</LastName>
<ForeName>Jun-Ichiro</ForeName>
<Initials>JI</Initials>
<AffiliationInfo><Affiliation>Research Center for Asian Infectious Diseases, Institute of Medical Science, The University of Tokyo, Tokyo, Japan jun-i@ims.u-tokyo.ac.jp zmatsuda@ims.u-tokyo.ac.jp.</Affiliation>
</AffiliationInfo>
<AffiliationInfo><Affiliation>Division of Cellular and Molecular Biology, Department of Cancer Biology, Institute of Medical Science, The University of Tokyo, Tokyo, Japan.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Matsuda</LastName>
<ForeName>Zene</ForeName>
<Initials>Z</Initials>
<AffiliationInfo><Affiliation>Research Center for Asian Infectious Diseases, Institute of Medical Science, The University of Tokyo, Tokyo, Japan jun-i@ims.u-tokyo.ac.jp zmatsuda@ims.u-tokyo.ac.jp.</Affiliation>
</AffiliationInfo>
<AffiliationInfo><Affiliation>Laboratory of Structural Virology and Immunology, Institute of Biophysics, Chinese Academy of Sciences, Beijing, People's Republic of China.</Affiliation>
</AffiliationInfo>
</Author>
</AuthorList>
<Language>eng</Language>
<PublicationTypeList><PublicationType UI="D016428">Journal Article</PublicationType>
<PublicationType UI="D013485">Research Support, Non-U.S. Gov't</PublicationType>
</PublicationTypeList>
<ArticleDate DateType="Electronic"><Year>2016</Year>
<Month>10</Month>
<Day>21</Day>
</ArticleDate>
</Article>
<MedlineJournalInfo><Country>United States</Country>
<MedlineTA>Antimicrob Agents Chemother</MedlineTA>
<NlmUniqueID>0315061</NlmUniqueID>
<ISSNLinking>0066-4804</ISSNLinking>
</MedlineJournalInfo>
<ChemicalList><Chemical><RegistryNumber>0</RegistryNumber>
<NameOfSubstance UI="D006146">Guanidines</NameOfSubstance>
</Chemical>
<Chemical><RegistryNumber>0</RegistryNumber>
<NameOfSubstance UI="D064370">Spike Glycoprotein, Coronavirus</NameOfSubstance>
</Chemical>
<Chemical><RegistryNumber>0</RegistryNumber>
<NameOfSubstance UI="D065147">Viral Fusion Protein Inhibitors</NameOfSubstance>
</Chemical>
<Chemical><RegistryNumber>EC 1.13.12.-</RegistryNumber>
<NameOfSubstance UI="D008156">Luciferases</NameOfSubstance>
</Chemical>
<Chemical><RegistryNumber>EC 3.4.-</RegistryNumber>
<NameOfSubstance UI="D002403">Cathepsins</NameOfSubstance>
</Chemical>
<Chemical><RegistryNumber>EC 3.4.14.5</RegistryNumber>
<NameOfSubstance UI="C042807">DPP4 protein, human</NameOfSubstance>
</Chemical>
<Chemical><RegistryNumber>EC 3.4.14.5</RegistryNumber>
<NameOfSubstance UI="D018819">Dipeptidyl Peptidase 4</NameOfSubstance>
</Chemical>
<Chemical><RegistryNumber>EC 3.4.21.-</RegistryNumber>
<NameOfSubstance UI="D012697">Serine Endopeptidases</NameOfSubstance>
</Chemical>
<Chemical><RegistryNumber>EC 3.4.21.-</RegistryNumber>
<NameOfSubstance UI="C421305">TMPRSS2 protein, human</NameOfSubstance>
</Chemical>
<Chemical><RegistryNumber>EC 3.4.21.75</RegistryNumber>
<NameOfSubstance UI="D045683">Furin</NameOfSubstance>
</Chemical>
<Chemical><RegistryNumber>Y25LQ0H97D</RegistryNumber>
<NameOfSubstance UI="C032855">nafamostat</NameOfSubstance>
</Chemical>
</ChemicalList>
<CitationSubset>IM</CitationSubset>
<MeshHeadingList><MeshHeading><DescriptorName UI="D002403" MajorTopicYN="N">Cathepsins</DescriptorName>
<QualifierName UI="Q000235" MajorTopicYN="N">genetics</QualifierName>
<QualifierName UI="Q000378" MajorTopicYN="N">metabolism</QualifierName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D002459" MajorTopicYN="N">Cell Fusion</DescriptorName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D002462" MajorTopicYN="N">Cell Membrane</DescriptorName>
<QualifierName UI="Q000187" MajorTopicYN="Y">drug effects</QualifierName>
<QualifierName UI="Q000378" MajorTopicYN="N">metabolism</QualifierName>
<QualifierName UI="Q000821" MajorTopicYN="N">virology</QualifierName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D018819" MajorTopicYN="N">Dipeptidyl Peptidase 4</DescriptorName>
<QualifierName UI="Q000235" MajorTopicYN="N">genetics</QualifierName>
<QualifierName UI="Q000378" MajorTopicYN="N">metabolism</QualifierName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D045683" MajorTopicYN="N">Furin</DescriptorName>
<QualifierName UI="Q000235" MajorTopicYN="N">genetics</QualifierName>
<QualifierName UI="Q000378" MajorTopicYN="N">metabolism</QualifierName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D005786" MajorTopicYN="N">Gene Expression Regulation</DescriptorName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D017930" MajorTopicYN="N">Genes, Reporter</DescriptorName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D006146" MajorTopicYN="N">Guanidines</DescriptorName>
<QualifierName UI="Q000494" MajorTopicYN="Y">pharmacology</QualifierName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D057809" MajorTopicYN="N">HEK293 Cells</DescriptorName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D057166" MajorTopicYN="N">High-Throughput Screening Assays</DescriptorName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D054884" MajorTopicYN="N">Host-Pathogen Interactions</DescriptorName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D006801" MajorTopicYN="N">Humans</DescriptorName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D007425" MajorTopicYN="N">Intracellular Membranes</DescriptorName>
<QualifierName UI="Q000187" MajorTopicYN="Y">drug effects</QualifierName>
<QualifierName UI="Q000378" MajorTopicYN="N">metabolism</QualifierName>
<QualifierName UI="Q000821" MajorTopicYN="N">virology</QualifierName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D008156" MajorTopicYN="N">Luciferases</DescriptorName>
<QualifierName UI="Q000235" MajorTopicYN="N">genetics</QualifierName>
<QualifierName UI="Q000378" MajorTopicYN="N">metabolism</QualifierName>
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<MeshHeading><DescriptorName UI="D008561" MajorTopicYN="N">Membrane Fusion</DescriptorName>
<QualifierName UI="Q000187" MajorTopicYN="Y">drug effects</QualifierName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D065207" MajorTopicYN="N">Middle East Respiratory Syndrome Coronavirus</DescriptorName>
<QualifierName UI="Q000187" MajorTopicYN="Y">drug effects</QualifierName>
<QualifierName UI="Q000235" MajorTopicYN="N">genetics</QualifierName>
<QualifierName UI="Q000254" MajorTopicYN="N">growth & development</QualifierName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D059748" MajorTopicYN="N">Proteolysis</DescriptorName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D012697" MajorTopicYN="N">Serine Endopeptidases</DescriptorName>
<QualifierName UI="Q000235" MajorTopicYN="N">genetics</QualifierName>
<QualifierName UI="Q000378" MajorTopicYN="N">metabolism</QualifierName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D064370" MajorTopicYN="N">Spike Glycoprotein, Coronavirus</DescriptorName>
<QualifierName UI="Q000037" MajorTopicYN="Y">antagonists & inhibitors</QualifierName>
<QualifierName UI="Q000235" MajorTopicYN="N">genetics</QualifierName>
<QualifierName UI="Q000378" MajorTopicYN="N">metabolism</QualifierName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D065147" MajorTopicYN="N">Viral Fusion Protein Inhibitors</DescriptorName>
<QualifierName UI="Q000494" MajorTopicYN="Y">pharmacology</QualifierName>
</MeshHeading>
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   |texte=   Identification of Nafamostat as a Potent Inhibitor of Middle East Respiratory Syndrome Coronavirus S Protein-Mediated Membrane Fusion Using the Split-Protein-Based Cell-Cell Fusion Assay.
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Identification of Nafamostat as a Potent Inhibitor of Middle East Respiratory Syndrome Coronavirus S Protein-Mediated Membrane Fusion Using the Split-Protein-Based Cell-Cell Fusion Assay.

Identification of Nafamostat as a Potent Inhibitor of Middle East Respiratory Syndrome Coronavirus S Protein-Mediated Membrane Fusion Using the Split-Protein-Based Cell-Cell Fusion Assay.

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