Structure-based discovery of Middle East respiratory syndrome coronavirus fusion inhibitor
Identifieur interne : 002819 ( Ncbi/Merge ); précédent : 002818; suivant : 002820Structure-based discovery of Middle East respiratory syndrome coronavirus fusion inhibitor
Auteurs : Lu Lu [République populaire de Chine] ; Qi Liu [République populaire de Chine] ; Yun Zhu [République populaire de Chine] ; Kwok-Hung Chan [Hong Kong] ; Lili Qin [République populaire de Chine] ; Yuan Li [République populaire de Chine] ; Qian Wang [République populaire de Chine] ; Jasper Fuk-Woo Chan [Hong Kong] ; Lanying Du [États-Unis] ; Fei Yu [États-Unis] ; Cuiqing Ma [États-Unis] ; Sheng Ye [République populaire de Chine] ; Kwok-Yung Yuen [Hong Kong] ; Rongguang Zhang [République populaire de Chine] ; Shibo Jiang [République populaire de Chine, États-Unis]Source :
- Nature Communications [ 2041-1723 ] ; 2014.
Descripteurs français
- KwdFr :
- Coronavirus du syndrome respiratoire du Moyen-Orient (métabolisme), Cristallographie aux rayons X, Données de séquences moléculaires, Glycoprotéine de spicule des coronavirus (), Glycoprotéine de spicule des coronavirus (métabolisme), Humains, Peptides (), Peptides (métabolisme), Protéines de fusion virale (antagonistes et inhibiteurs), Protéines de fusion virale (métabolisme), Protéines virales (), Protéines virales (métabolisme), Pénétration virale, Réplication virale, Séquence d'acides aminés.
- MESH :
- antagonistes et inhibiteurs : Protéines de fusion virale.
- métabolisme : Coronavirus du syndrome respiratoire du Moyen-Orient, Glycoprotéine de spicule des coronavirus, Peptides, Protéines de fusion virale, Protéines virales.
- Cristallographie aux rayons X, Données de séquences moléculaires, Glycoprotéine de spicule des coronavirus, Humains, Peptides, Protéines virales, Pénétration virale, Réplication virale, Séquence d'acides aminés.
English descriptors
- KwdEn :
- Amino Acid Sequence, Crystallography, X-Ray, Humans, Middle East Respiratory Syndrome Coronavirus (metabolism), Molecular Sequence Data, Peptides (chemistry), Peptides (metabolism), Spike Glycoprotein, Coronavirus (chemistry), Spike Glycoprotein, Coronavirus (metabolism), Viral Fusion Proteins (antagonists & inhibitors), Viral Fusion Proteins (metabolism), Viral Proteins (chemistry), Viral Proteins (metabolism), Virus Internalization, Virus Replication.
- MESH :
- chemical , antagonists & inhibitors : Viral Fusion Proteins.
- chemical , chemistry : Peptides, Spike Glycoprotein, Coronavirus, Viral Proteins.
- metabolism : Middle East Respiratory Syndrome Coronavirus, Peptides, Spike Glycoprotein, Coronavirus, Viral Fusion Proteins, Viral Proteins.
- Amino Acid Sequence, Crystallography, X-Ray, Humans, Molecular Sequence Data, Virus Internalization, Virus Replication.
Abstract
A novel human coronavirus, Middle East respiratory syndrome coronavirus (MERS-CoV), has caused outbreaks of a SARS-like illness with high case fatality rate. The reports of its person-to-person transmission through close contacts have raised a global concern about its pandemic potential. Here we characterize the six-helix bundle fusion core structure of MERS-CoV spike protein S2 subunit by X-ray crystallography and biophysical analysis. We find that two peptides, HR1P and HR2P, spanning residues 998–1039 in HR1 and 1251–1286 in HR2 domains, respectively, can form a stable six-helix bundle fusion core structure, suggesting that MERS-CoV enters into the host cell mainly through membrane fusion mechanism. HR2P can effectively inhibit MERS-CoV replication and its spike protein-mediated cell–cell fusion. Introduction of hydrophilic residues into HR2P results in significant improvement of its stability, solubility and antiviral activity. Therefore, the HR2P analogues have good potential to be further developed into effective viral fusion inhibitors for treating MERS-CoV infection.
The online version of this article (doi:10.1038/ncomms4067) contains supplementary material, which is available to authorized users.
Url:
DOI: 10.1038/ncomms4067
PubMed: 24473083
PubMed Central: 7091805
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PMC:7091805Le document en format XML
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<sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">Structure-based discovery of Middle East respiratory syndrome coronavirus fusion inhibitor</title>
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<region type="state">État de New York</region>
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<wicri:regionArea>New York</wicri:regionArea>
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<author><name sortKey="Ma, Cuiqing" sort="Ma, Cuiqing" uniqKey="Ma C" first="Cuiqing" last="Ma">Cuiqing Ma</name>
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<institution>Lindsley F. Kimball Research Institute, New York Blood Center,</institution>
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New York, 10065 New York USA</nlm:aff>
<country>États-Unis</country>
<placeName><settlement type="city">New York</settlement>
<region type="state">État de New York</region>
</placeName>
<wicri:regionArea>New York</wicri:regionArea>
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<author><name sortKey="Ye, Sheng" sort="Ye, Sheng" uniqKey="Ye S" first="Sheng" last="Ye">Sheng Ye</name>
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<institution>National Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences,</institution>
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Beijing, 100101 China</nlm:aff>
<country xml:lang="fr">République populaire de Chine</country>
<wicri:regionArea>Beijing</wicri:regionArea>
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<author><name sortKey="Yuen, Kwok Yung" sort="Yuen, Kwok Yung" uniqKey="Yuen K" first="Kwok-Yung" last="Yuen">Kwok-Yung Yuen</name>
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<institution-id institution-id-type="ISNI">0000000121742757</institution-id>
<institution>Department of Microbiology,</institution>
<institution>State Key Laboratory of Emerging Infectious Diseases, Carol Yu Centre for Infection, The University of Hong Kong,</institution>
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Pokfulam, Hong Kong</nlm:aff>
<country xml:lang="fr">Hong Kong</country>
<wicri:regionArea>Pokfulam</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Zhang, Rongguang" sort="Zhang, Rongguang" uniqKey="Zhang R" first="Rongguang" last="Zhang">Rongguang Zhang</name>
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<institution-id institution-id-type="ISNI">0000 0004 1792 5640</institution-id>
<institution>National Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences,</institution>
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Beijing, 100101 China</nlm:aff>
<country xml:lang="fr">République populaire de Chine</country>
<wicri:regionArea>Beijing</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Jiang, Shibo" sort="Jiang, Shibo" uniqKey="Jiang S" first="Shibo" last="Jiang">Shibo Jiang</name>
<affiliation wicri:level="1"><nlm:aff id="Aff1"><institution-wrap><institution-id institution-id-type="GRID">grid.8547.e</institution-id>
<institution-id institution-id-type="ISNI">0000 0001 0125 2443</institution-id>
<institution>Key Laboratory of Medical Molecular Virology of Ministries of Education and Health, Shanghai Medical College and Institute of Medical Microbiology, Fudan University,</institution>
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Shanghai, 200032 China</nlm:aff>
<country xml:lang="fr">République populaire de Chine</country>
<wicri:regionArea>Shanghai</wicri:regionArea>
</affiliation>
<affiliation wicri:level="1"><nlm:aff id="Aff4"><institution-wrap><institution-id institution-id-type="GRID">grid.250415.7</institution-id>
<institution-id institution-id-type="ISNI">0000 0004 0442 2075</institution-id>
<institution>Lindsley F. Kimball Research Institute, New York Blood Center,</institution>
</institution-wrap>
New York, 10065 New York USA</nlm:aff>
<country>États-Unis</country>
<placeName><settlement type="city">New York</settlement>
<region type="state">État de New York</region>
</placeName>
<wicri:regionArea>New York</wicri:regionArea>
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</author>
</analytic>
<series><title level="j">Nature Communications</title>
<idno type="eISSN">2041-1723</idno>
<imprint><date when="2014">2014</date>
</imprint>
</series>
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<profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Amino Acid Sequence</term>
<term>Crystallography, X-Ray</term>
<term>Humans</term>
<term>Middle East Respiratory Syndrome Coronavirus (metabolism)</term>
<term>Molecular Sequence Data</term>
<term>Peptides (chemistry)</term>
<term>Peptides (metabolism)</term>
<term>Spike Glycoprotein, Coronavirus (chemistry)</term>
<term>Spike Glycoprotein, Coronavirus (metabolism)</term>
<term>Viral Fusion Proteins (antagonists & inhibitors)</term>
<term>Viral Fusion Proteins (metabolism)</term>
<term>Viral Proteins (chemistry)</term>
<term>Viral Proteins (metabolism)</term>
<term>Virus Internalization</term>
<term>Virus Replication</term>
</keywords>
<keywords scheme="KwdFr" xml:lang="fr"><term>Coronavirus du syndrome respiratoire du Moyen-Orient (métabolisme)</term>
<term>Cristallographie aux rayons X</term>
<term>Données de séquences moléculaires</term>
<term>Glycoprotéine de spicule des coronavirus ()</term>
<term>Glycoprotéine de spicule des coronavirus (métabolisme)</term>
<term>Humains</term>
<term>Peptides ()</term>
<term>Peptides (métabolisme)</term>
<term>Protéines de fusion virale (antagonistes et inhibiteurs)</term>
<term>Protéines de fusion virale (métabolisme)</term>
<term>Protéines virales ()</term>
<term>Protéines virales (métabolisme)</term>
<term>Pénétration virale</term>
<term>Réplication virale</term>
<term>Séquence d'acides aminés</term>
</keywords>
<keywords scheme="MESH" type="chemical" qualifier="antagonists & inhibitors" xml:lang="en"><term>Viral Fusion Proteins</term>
</keywords>
<keywords scheme="MESH" type="chemical" qualifier="chemistry" xml:lang="en"><term>Peptides</term>
<term>Spike Glycoprotein, Coronavirus</term>
<term>Viral Proteins</term>
</keywords>
<keywords scheme="MESH" qualifier="antagonistes et inhibiteurs" xml:lang="fr"><term>Protéines de fusion virale</term>
</keywords>
<keywords scheme="MESH" qualifier="metabolism" xml:lang="en"><term>Middle East Respiratory Syndrome Coronavirus</term>
<term>Peptides</term>
<term>Spike Glycoprotein, Coronavirus</term>
<term>Viral Fusion Proteins</term>
<term>Viral Proteins</term>
</keywords>
<keywords scheme="MESH" qualifier="métabolisme" xml:lang="fr"><term>Coronavirus du syndrome respiratoire du Moyen-Orient</term>
<term>Glycoprotéine de spicule des coronavirus</term>
<term>Peptides</term>
<term>Protéines de fusion virale</term>
<term>Protéines virales</term>
</keywords>
<keywords scheme="MESH" xml:lang="en"><term>Amino Acid Sequence</term>
<term>Crystallography, X-Ray</term>
<term>Humans</term>
<term>Molecular Sequence Data</term>
<term>Virus Internalization</term>
<term>Virus Replication</term>
</keywords>
<keywords scheme="MESH" xml:lang="fr"><term>Cristallographie aux rayons X</term>
<term>Données de séquences moléculaires</term>
<term>Glycoprotéine de spicule des coronavirus</term>
<term>Humains</term>
<term>Peptides</term>
<term>Protéines virales</term>
<term>Pénétration virale</term>
<term>Réplication virale</term>
<term>Séquence d'acides aminés</term>
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<front><div type="abstract" xml:lang="en"><p id="Par1">A novel human coronavirus, Middle East respiratory syndrome coronavirus (MERS-CoV), has caused outbreaks of a SARS-like illness with high case fatality rate. The reports of its person-to-person transmission through close contacts have raised a global concern about its pandemic potential. Here we characterize the six-helix bundle fusion core structure of MERS-CoV spike protein S2 subunit by X-ray crystallography and biophysical analysis. We find that two peptides, HR1P and HR2P, spanning residues 998–1039 in HR1 and 1251–1286 in HR2 domains, respectively, can form a stable six-helix bundle fusion core structure, suggesting that MERS-CoV enters into the host cell mainly through membrane fusion mechanism. HR2P can effectively inhibit MERS-CoV replication and its spike protein-mediated cell–cell fusion. Introduction of hydrophilic residues into HR2P results in significant improvement of its stability, solubility and antiviral activity. Therefore, the HR2P analogues have good potential to be further developed into effective viral fusion inhibitors for treating MERS-CoV infection.</p>
<sec><title>Supplementary information</title>
<p>The online version of this article (doi:10.1038/ncomms4067) contains supplementary material, which is available to authorized users.</p>
</sec>
</div>
</front>
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Shanghai, 200032 China</nlm:aff>
<country xml:lang="fr">République populaire de Chine</country>
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<author><name sortKey="Liu, Qi" sort="Liu, Qi" uniqKey="Liu Q" first="Qi" last="Liu">Qi Liu</name>
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Shanghai, 200032 China</nlm:aff>
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Pokfulam, Hong Kong</nlm:aff>
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<author><name sortKey="Chan, Jasper Fuk Woo" sort="Chan, Jasper Fuk Woo" uniqKey="Chan J" first="Jasper Fuk-Woo" last="Chan">Jasper Fuk-Woo Chan</name>
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<country xml:lang="fr">Hong Kong</country>
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</author>
<author><name sortKey="Du, Lanying" sort="Du, Lanying" uniqKey="Du L" first="Lanying" last="Du">Lanying Du</name>
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<author><name sortKey="Yu, Fei" sort="Yu, Fei" uniqKey="Yu F" first="Fei" last="Yu">Fei Yu</name>
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<author><name sortKey="Ye, Sheng" sort="Ye, Sheng" uniqKey="Ye S" first="Sheng" last="Ye">Sheng Ye</name>
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</author>
<author><name sortKey="Yuen, Kwok Yung" sort="Yuen, Kwok Yung" uniqKey="Yuen K" first="Kwok-Yung" last="Yuen">Kwok-Yung Yuen</name>
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<country xml:lang="fr">Hong Kong</country>
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</author>
<author><name sortKey="Zhang, Rongguang" sort="Zhang, Rongguang" uniqKey="Zhang R" first="Rongguang" last="Zhang">Rongguang Zhang</name>
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</institution-wrap>
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<sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">Structure-based discovery of Middle East respiratory syndrome coronavirus fusion inhibitor</title>
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Shanghai, 200032 China</nlm:aff>
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</author>
<author><name sortKey="Liu, Qi" sort="Liu, Qi" uniqKey="Liu Q" first="Qi" last="Liu">Qi Liu</name>
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</institution-wrap>
Shanghai, 200032 China</nlm:aff>
<country xml:lang="fr">République populaire de Chine</country>
<wicri:regionArea>Shanghai</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Zhu, Yun" sort="Zhu, Yun" uniqKey="Zhu Y" first="Yun" last="Zhu">Yun Zhu</name>
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Beijing, 100101 China</nlm:aff>
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<wicri:regionArea>Beijing</wicri:regionArea>
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<author><name sortKey="Chan, Kwok Hung" sort="Chan, Kwok Hung" uniqKey="Chan K" first="Kwok-Hung" last="Chan">Kwok-Hung Chan</name>
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Beijing, 100101 China</nlm:aff>
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<author><name sortKey="Li, Yuan" sort="Li, Yuan" uniqKey="Li Y" first="Yuan" last="Li">Yuan Li</name>
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Shanghai, 200032 China</nlm:aff>
<country xml:lang="fr">République populaire de Chine</country>
<wicri:regionArea>Shanghai</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Wang, Qian" sort="Wang, Qian" uniqKey="Wang Q" first="Qian" last="Wang">Qian Wang</name>
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</institution-wrap>
Shanghai, 200032 China</nlm:aff>
<country xml:lang="fr">République populaire de Chine</country>
<wicri:regionArea>Shanghai</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Chan, Jasper Fuk Woo" sort="Chan, Jasper Fuk Woo" uniqKey="Chan J" first="Jasper Fuk-Woo" last="Chan">Jasper Fuk-Woo Chan</name>
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<institution>Department of Microbiology,</institution>
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</institution-wrap>
Pokfulam, Hong Kong</nlm:aff>
<country xml:lang="fr">Hong Kong</country>
<wicri:regionArea>Pokfulam</wicri:regionArea>
</affiliation>
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<author><name sortKey="Du, Lanying" sort="Du, Lanying" uniqKey="Du L" first="Lanying" last="Du">Lanying Du</name>
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</institution-wrap>
New York, 10065 New York USA</nlm:aff>
<country>États-Unis</country>
<placeName><settlement type="city">New York</settlement>
<region type="state">État de New York</region>
</placeName>
<wicri:regionArea>New York</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Yu, Fei" sort="Yu, Fei" uniqKey="Yu F" first="Fei" last="Yu">Fei Yu</name>
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New York, 10065 New York USA</nlm:aff>
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<region type="state">État de New York</region>
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New York, 10065 New York USA</nlm:aff>
<country>États-Unis</country>
<placeName><settlement type="city">New York</settlement>
<region type="state">État de New York</region>
</placeName>
<wicri:regionArea>New York</wicri:regionArea>
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<author><name sortKey="Ye, Sheng" sort="Ye, Sheng" uniqKey="Ye S" first="Sheng" last="Ye">Sheng Ye</name>
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</institution-wrap>
Beijing, 100101 China</nlm:aff>
<country xml:lang="fr">République populaire de Chine</country>
<wicri:regionArea>Beijing</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Yuen, Kwok Yung" sort="Yuen, Kwok Yung" uniqKey="Yuen K" first="Kwok-Yung" last="Yuen">Kwok-Yung Yuen</name>
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<institution-id institution-id-type="ISNI">0000000121742757</institution-id>
<institution>Department of Microbiology,</institution>
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</institution-wrap>
Pokfulam, Hong Kong</nlm:aff>
<country xml:lang="fr">Hong Kong</country>
<wicri:regionArea>Pokfulam</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Zhang, Rongguang" sort="Zhang, Rongguang" uniqKey="Zhang R" first="Rongguang" last="Zhang">Rongguang Zhang</name>
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<institution>National Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences,</institution>
</institution-wrap>
Beijing, 100101 China</nlm:aff>
<country xml:lang="fr">République populaire de Chine</country>
<wicri:regionArea>Beijing</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Jiang, Shibo" sort="Jiang, Shibo" uniqKey="Jiang S" first="Shibo" last="Jiang">Shibo Jiang</name>
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Shanghai, 200032 China</nlm:aff>
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New York, 10065 New York USA</nlm:aff>
<country>États-Unis</country>
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<wicri:regionArea>New York</wicri:regionArea>
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<series><title level="j">Nature Communications</title>
<idno type="eISSN">2041-1723</idno>
<imprint><date when="2014">2014</date>
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<front><div type="abstract" xml:lang="en"><p id="Par1">A novel human coronavirus, Middle East respiratory syndrome coronavirus (MERS-CoV), has caused outbreaks of a SARS-like illness with high case fatality rate. The reports of its person-to-person transmission through close contacts have raised a global concern about its pandemic potential. Here we characterize the six-helix bundle fusion core structure of MERS-CoV spike protein S2 subunit by X-ray crystallography and biophysical analysis. We find that two peptides, HR1P and HR2P, spanning residues 998–1039 in HR1 and 1251–1286 in HR2 domains, respectively, can form a stable six-helix bundle fusion core structure, suggesting that MERS-CoV enters into the host cell mainly through membrane fusion mechanism. HR2P can effectively inhibit MERS-CoV replication and its spike protein-mediated cell–cell fusion. Introduction of hydrophilic residues into HR2P results in significant improvement of its stability, solubility and antiviral activity. Therefore, the HR2P analogues have good potential to be further developed into effective viral fusion inhibitors for treating MERS-CoV infection.</p>
<sec><title>Supplementary information</title>
<p>The online version of this article (doi:10.1038/ncomms4067) contains supplementary material, which is available to authorized users.</p>
</sec>
</div>
</front>
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<pubmed><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">Structure-based discovery of Middle East respiratory syndrome coronavirus fusion inhibitor.</title>
<author><name sortKey="Lu, Lu" sort="Lu, Lu" uniqKey="Lu L" first="Lu" last="Lu">Lu Lu</name>
<affiliation><nlm:affiliation>1] Key Laboratory of Medical Molecular Virology of Ministries of Education and Health, Shanghai Medical College and Institute of Medical Microbiology, Fudan University, Shanghai 200032, China [2].</nlm:affiliation>
<wicri:noCountry code="subField">China [2]</wicri:noCountry>
</affiliation>
</author>
<author><name sortKey="Liu, Qi" sort="Liu, Qi" uniqKey="Liu Q" first="Qi" last="Liu">Qi Liu</name>
<affiliation><nlm:affiliation>1] Key Laboratory of Medical Molecular Virology of Ministries of Education and Health, Shanghai Medical College and Institute of Medical Microbiology, Fudan University, Shanghai 200032, China [2].</nlm:affiliation>
<wicri:noCountry code="subField">China [2]</wicri:noCountry>
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</author>
<author><name sortKey="Zhu, Yun" sort="Zhu, Yun" uniqKey="Zhu Y" first="Yun" last="Zhu">Yun Zhu</name>
<affiliation><nlm:affiliation>1] National Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China [2].</nlm:affiliation>
<wicri:noCountry code="subField">China [2]</wicri:noCountry>
</affiliation>
</author>
<author><name sortKey="Chan, Kwok Hung" sort="Chan, Kwok Hung" uniqKey="Chan K" first="Kwok-Hung" last="Chan">Kwok-Hung Chan</name>
<affiliation wicri:level="1"><nlm:affiliation>State Key Laboratory of Emerging Infectious Diseases, Carol Yu Centre for Infection, Department of Microbiology, The University of Hong Kong, Pokfulam, Hong Kong.</nlm:affiliation>
<country xml:lang="fr">Hong Kong</country>
<wicri:regionArea>State Key Laboratory of Emerging Infectious Diseases, Carol Yu Centre for Infection, Department of Microbiology, The University of Hong Kong, Pokfulam</wicri:regionArea>
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</author>
<author><name sortKey="Qin, Lili" sort="Qin, Lili" uniqKey="Qin L" first="Lili" last="Qin">Lili Qin</name>
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<country xml:lang="fr">République populaire de Chine</country>
<wicri:regionArea>National Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101</wicri:regionArea>
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</author>
<author><name sortKey="Li, Yuan" sort="Li, Yuan" uniqKey="Li Y" first="Yuan" last="Li">Yuan Li</name>
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<country xml:lang="fr">République populaire de Chine</country>
<wicri:regionArea>Key Laboratory of Medical Molecular Virology of Ministries of Education and Health, Shanghai Medical College and Institute of Medical Microbiology, Fudan University, Shanghai 200032</wicri:regionArea>
<wicri:noRegion>Shanghai 200032</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Wang, Qian" sort="Wang, Qian" uniqKey="Wang Q" first="Qian" last="Wang">Qian Wang</name>
<affiliation wicri:level="1"><nlm:affiliation>Key Laboratory of Medical Molecular Virology of Ministries of Education and Health, Shanghai Medical College and Institute of Medical Microbiology, Fudan University, Shanghai 200032, China.</nlm:affiliation>
<country xml:lang="fr">République populaire de Chine</country>
<wicri:regionArea>Key Laboratory of Medical Molecular Virology of Ministries of Education and Health, Shanghai Medical College and Institute of Medical Microbiology, Fudan University, Shanghai 200032</wicri:regionArea>
<wicri:noRegion>Shanghai 200032</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Chan, Jasper Fuk Woo" sort="Chan, Jasper Fuk Woo" uniqKey="Chan J" first="Jasper Fuk-Woo" last="Chan">Jasper Fuk-Woo Chan</name>
<affiliation wicri:level="1"><nlm:affiliation>State Key Laboratory of Emerging Infectious Diseases, Carol Yu Centre for Infection, Department of Microbiology, The University of Hong Kong, Pokfulam, Hong Kong.</nlm:affiliation>
<country xml:lang="fr">Hong Kong</country>
<wicri:regionArea>State Key Laboratory of Emerging Infectious Diseases, Carol Yu Centre for Infection, Department of Microbiology, The University of Hong Kong, Pokfulam</wicri:regionArea>
<wicri:noRegion>Pokfulam</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Du, Lanying" sort="Du, Lanying" uniqKey="Du L" first="Lanying" last="Du">Lanying Du</name>
<affiliation wicri:level="1"><nlm:affiliation>Lindsley F. Kimball Research Institute, New York Blood Center, New York, New York 10065, USA.</nlm:affiliation>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Lindsley F. Kimball Research Institute, New York Blood Center, New York, New York 10065</wicri:regionArea>
<wicri:noRegion>New York 10065</wicri:noRegion>
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<author><name sortKey="Yu, Fei" sort="Yu, Fei" uniqKey="Yu F" first="Fei" last="Yu">Fei Yu</name>
<affiliation wicri:level="1"><nlm:affiliation>Lindsley F. Kimball Research Institute, New York Blood Center, New York, New York 10065, USA.</nlm:affiliation>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Lindsley F. Kimball Research Institute, New York Blood Center, New York, New York 10065</wicri:regionArea>
<wicri:noRegion>New York 10065</wicri:noRegion>
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<author><name sortKey="Ma, Cuiqing" sort="Ma, Cuiqing" uniqKey="Ma C" first="Cuiqing" last="Ma">Cuiqing Ma</name>
<affiliation wicri:level="1"><nlm:affiliation>Lindsley F. Kimball Research Institute, New York Blood Center, New York, New York 10065, USA.</nlm:affiliation>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Lindsley F. Kimball Research Institute, New York Blood Center, New York, New York 10065</wicri:regionArea>
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<author><name sortKey="Ye, Sheng" sort="Ye, Sheng" uniqKey="Ye S" first="Sheng" last="Ye">Sheng Ye</name>
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<country xml:lang="fr">République populaire de Chine</country>
<wicri:regionArea>National Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101</wicri:regionArea>
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</author>
<author><name sortKey="Yuen, Kwok Yung" sort="Yuen, Kwok Yung" uniqKey="Yuen K" first="Kwok-Yung" last="Yuen">Kwok-Yung Yuen</name>
<affiliation wicri:level="1"><nlm:affiliation>State Key Laboratory of Emerging Infectious Diseases, Carol Yu Centre for Infection, Department of Microbiology, The University of Hong Kong, Pokfulam, Hong Kong.</nlm:affiliation>
<country xml:lang="fr">Hong Kong</country>
<wicri:regionArea>State Key Laboratory of Emerging Infectious Diseases, Carol Yu Centre for Infection, Department of Microbiology, The University of Hong Kong, Pokfulam</wicri:regionArea>
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</affiliation>
</author>
<author><name sortKey="Zhang, Rongguang" sort="Zhang, Rongguang" uniqKey="Zhang R" first="Rongguang" last="Zhang">Rongguang Zhang</name>
<affiliation wicri:level="1"><nlm:affiliation>National Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China.</nlm:affiliation>
<country xml:lang="fr">République populaire de Chine</country>
<wicri:regionArea>National Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101</wicri:regionArea>
<placeName><settlement type="city">Pékin</settlement>
</placeName>
</affiliation>
</author>
<author><name sortKey="Jiang, Shibo" sort="Jiang, Shibo" uniqKey="Jiang S" first="Shibo" last="Jiang">Shibo Jiang</name>
<affiliation wicri:level="1"><nlm:affiliation>1] Key Laboratory of Medical Molecular Virology of Ministries of Education and Health, Shanghai Medical College and Institute of Medical Microbiology, Fudan University, Shanghai 200032, China [2] Lindsley F. Kimball Research Institute, New York Blood Center, New York, New York 10065, USA.</nlm:affiliation>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>1] Key Laboratory of Medical Molecular Virology of Ministries of Education and Health, Shanghai Medical College and Institute of Medical Microbiology, Fudan University, Shanghai 200032, China [2] Lindsley F. Kimball Research Institute, New York Blood Center, New York, New York 10065</wicri:regionArea>
<wicri:noRegion>New York 10065</wicri:noRegion>
</affiliation>
</author>
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<date when="2014">2014</date>
<idno type="RBID">pubmed:24473083</idno>
<idno type="pmid">24473083</idno>
<idno type="doi">10.1038/ncomms4067</idno>
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<sourceDesc><biblStruct><analytic><title xml:lang="en">Structure-based discovery of Middle East respiratory syndrome coronavirus fusion inhibitor.</title>
<author><name sortKey="Lu, Lu" sort="Lu, Lu" uniqKey="Lu L" first="Lu" last="Lu">Lu Lu</name>
<affiliation><nlm:affiliation>1] Key Laboratory of Medical Molecular Virology of Ministries of Education and Health, Shanghai Medical College and Institute of Medical Microbiology, Fudan University, Shanghai 200032, China [2].</nlm:affiliation>
<wicri:noCountry code="subField">China [2]</wicri:noCountry>
</affiliation>
</author>
<author><name sortKey="Liu, Qi" sort="Liu, Qi" uniqKey="Liu Q" first="Qi" last="Liu">Qi Liu</name>
<affiliation><nlm:affiliation>1] Key Laboratory of Medical Molecular Virology of Ministries of Education and Health, Shanghai Medical College and Institute of Medical Microbiology, Fudan University, Shanghai 200032, China [2].</nlm:affiliation>
<wicri:noCountry code="subField">China [2]</wicri:noCountry>
</affiliation>
</author>
<author><name sortKey="Zhu, Yun" sort="Zhu, Yun" uniqKey="Zhu Y" first="Yun" last="Zhu">Yun Zhu</name>
<affiliation><nlm:affiliation>1] National Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China [2].</nlm:affiliation>
<wicri:noCountry code="subField">China [2]</wicri:noCountry>
</affiliation>
</author>
<author><name sortKey="Chan, Kwok Hung" sort="Chan, Kwok Hung" uniqKey="Chan K" first="Kwok-Hung" last="Chan">Kwok-Hung Chan</name>
<affiliation wicri:level="1"><nlm:affiliation>State Key Laboratory of Emerging Infectious Diseases, Carol Yu Centre for Infection, Department of Microbiology, The University of Hong Kong, Pokfulam, Hong Kong.</nlm:affiliation>
<country xml:lang="fr">Hong Kong</country>
<wicri:regionArea>State Key Laboratory of Emerging Infectious Diseases, Carol Yu Centre for Infection, Department of Microbiology, The University of Hong Kong, Pokfulam</wicri:regionArea>
<wicri:noRegion>Pokfulam</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Qin, Lili" sort="Qin, Lili" uniqKey="Qin L" first="Lili" last="Qin">Lili Qin</name>
<affiliation wicri:level="1"><nlm:affiliation>National Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China.</nlm:affiliation>
<country xml:lang="fr">République populaire de Chine</country>
<wicri:regionArea>National Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101</wicri:regionArea>
<placeName><settlement type="city">Pékin</settlement>
</placeName>
</affiliation>
</author>
<author><name sortKey="Li, Yuan" sort="Li, Yuan" uniqKey="Li Y" first="Yuan" last="Li">Yuan Li</name>
<affiliation wicri:level="1"><nlm:affiliation>Key Laboratory of Medical Molecular Virology of Ministries of Education and Health, Shanghai Medical College and Institute of Medical Microbiology, Fudan University, Shanghai 200032, China.</nlm:affiliation>
<country xml:lang="fr">République populaire de Chine</country>
<wicri:regionArea>Key Laboratory of Medical Molecular Virology of Ministries of Education and Health, Shanghai Medical College and Institute of Medical Microbiology, Fudan University, Shanghai 200032</wicri:regionArea>
<wicri:noRegion>Shanghai 200032</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Wang, Qian" sort="Wang, Qian" uniqKey="Wang Q" first="Qian" last="Wang">Qian Wang</name>
<affiliation wicri:level="1"><nlm:affiliation>Key Laboratory of Medical Molecular Virology of Ministries of Education and Health, Shanghai Medical College and Institute of Medical Microbiology, Fudan University, Shanghai 200032, China.</nlm:affiliation>
<country xml:lang="fr">République populaire de Chine</country>
<wicri:regionArea>Key Laboratory of Medical Molecular Virology of Ministries of Education and Health, Shanghai Medical College and Institute of Medical Microbiology, Fudan University, Shanghai 200032</wicri:regionArea>
<wicri:noRegion>Shanghai 200032</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Chan, Jasper Fuk Woo" sort="Chan, Jasper Fuk Woo" uniqKey="Chan J" first="Jasper Fuk-Woo" last="Chan">Jasper Fuk-Woo Chan</name>
<affiliation wicri:level="1"><nlm:affiliation>State Key Laboratory of Emerging Infectious Diseases, Carol Yu Centre for Infection, Department of Microbiology, The University of Hong Kong, Pokfulam, Hong Kong.</nlm:affiliation>
<country xml:lang="fr">Hong Kong</country>
<wicri:regionArea>State Key Laboratory of Emerging Infectious Diseases, Carol Yu Centre for Infection, Department of Microbiology, The University of Hong Kong, Pokfulam</wicri:regionArea>
<wicri:noRegion>Pokfulam</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Du, Lanying" sort="Du, Lanying" uniqKey="Du L" first="Lanying" last="Du">Lanying Du</name>
<affiliation wicri:level="1"><nlm:affiliation>Lindsley F. Kimball Research Institute, New York Blood Center, New York, New York 10065, USA.</nlm:affiliation>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Lindsley F. Kimball Research Institute, New York Blood Center, New York, New York 10065</wicri:regionArea>
<wicri:noRegion>New York 10065</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Yu, Fei" sort="Yu, Fei" uniqKey="Yu F" first="Fei" last="Yu">Fei Yu</name>
<affiliation wicri:level="1"><nlm:affiliation>Lindsley F. Kimball Research Institute, New York Blood Center, New York, New York 10065, USA.</nlm:affiliation>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Lindsley F. Kimball Research Institute, New York Blood Center, New York, New York 10065</wicri:regionArea>
<wicri:noRegion>New York 10065</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Ma, Cuiqing" sort="Ma, Cuiqing" uniqKey="Ma C" first="Cuiqing" last="Ma">Cuiqing Ma</name>
<affiliation wicri:level="1"><nlm:affiliation>Lindsley F. Kimball Research Institute, New York Blood Center, New York, New York 10065, USA.</nlm:affiliation>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Lindsley F. Kimball Research Institute, New York Blood Center, New York, New York 10065</wicri:regionArea>
<wicri:noRegion>New York 10065</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Ye, Sheng" sort="Ye, Sheng" uniqKey="Ye S" first="Sheng" last="Ye">Sheng Ye</name>
<affiliation wicri:level="1"><nlm:affiliation>National Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China.</nlm:affiliation>
<country xml:lang="fr">République populaire de Chine</country>
<wicri:regionArea>National Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101</wicri:regionArea>
<placeName><settlement type="city">Pékin</settlement>
</placeName>
</affiliation>
</author>
<author><name sortKey="Yuen, Kwok Yung" sort="Yuen, Kwok Yung" uniqKey="Yuen K" first="Kwok-Yung" last="Yuen">Kwok-Yung Yuen</name>
<affiliation wicri:level="1"><nlm:affiliation>State Key Laboratory of Emerging Infectious Diseases, Carol Yu Centre for Infection, Department of Microbiology, The University of Hong Kong, Pokfulam, Hong Kong.</nlm:affiliation>
<country xml:lang="fr">Hong Kong</country>
<wicri:regionArea>State Key Laboratory of Emerging Infectious Diseases, Carol Yu Centre for Infection, Department of Microbiology, The University of Hong Kong, Pokfulam</wicri:regionArea>
<wicri:noRegion>Pokfulam</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Zhang, Rongguang" sort="Zhang, Rongguang" uniqKey="Zhang R" first="Rongguang" last="Zhang">Rongguang Zhang</name>
<affiliation wicri:level="1"><nlm:affiliation>National Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China.</nlm:affiliation>
<country xml:lang="fr">République populaire de Chine</country>
<wicri:regionArea>National Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101</wicri:regionArea>
<placeName><settlement type="city">Pékin</settlement>
</placeName>
</affiliation>
</author>
<author><name sortKey="Jiang, Shibo" sort="Jiang, Shibo" uniqKey="Jiang S" first="Shibo" last="Jiang">Shibo Jiang</name>
<affiliation wicri:level="1"><nlm:affiliation>1] Key Laboratory of Medical Molecular Virology of Ministries of Education and Health, Shanghai Medical College and Institute of Medical Microbiology, Fudan University, Shanghai 200032, China [2] Lindsley F. Kimball Research Institute, New York Blood Center, New York, New York 10065, USA.</nlm:affiliation>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>1] Key Laboratory of Medical Molecular Virology of Ministries of Education and Health, Shanghai Medical College and Institute of Medical Microbiology, Fudan University, Shanghai 200032, China [2] Lindsley F. Kimball Research Institute, New York Blood Center, New York, New York 10065</wicri:regionArea>
<wicri:noRegion>New York 10065</wicri:noRegion>
</affiliation>
</author>
</analytic>
<series><title level="j">Nature communications</title>
<idno type="eISSN">2041-1723</idno>
<imprint><date when="2014" type="published">2014</date>
</imprint>
</series>
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</sourceDesc>
</fileDesc>
<profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Amino Acid Sequence</term>
<term>Crystallography, X-Ray</term>
<term>Humans</term>
<term>Middle East Respiratory Syndrome Coronavirus (metabolism)</term>
<term>Molecular Sequence Data</term>
<term>Peptides (chemistry)</term>
<term>Peptides (metabolism)</term>
<term>Spike Glycoprotein, Coronavirus (chemistry)</term>
<term>Spike Glycoprotein, Coronavirus (metabolism)</term>
<term>Viral Fusion Proteins (antagonists & inhibitors)</term>
<term>Viral Fusion Proteins (metabolism)</term>
<term>Viral Proteins (chemistry)</term>
<term>Viral Proteins (metabolism)</term>
<term>Virus Internalization</term>
<term>Virus Replication</term>
</keywords>
<keywords scheme="KwdFr" xml:lang="fr"><term>Coronavirus du syndrome respiratoire du Moyen-Orient (métabolisme)</term>
<term>Cristallographie aux rayons X</term>
<term>Données de séquences moléculaires</term>
<term>Glycoprotéine de spicule des coronavirus ()</term>
<term>Glycoprotéine de spicule des coronavirus (métabolisme)</term>
<term>Humains</term>
<term>Peptides ()</term>
<term>Peptides (métabolisme)</term>
<term>Protéines de fusion virale (antagonistes et inhibiteurs)</term>
<term>Protéines de fusion virale (métabolisme)</term>
<term>Protéines virales ()</term>
<term>Protéines virales (métabolisme)</term>
<term>Pénétration virale</term>
<term>Réplication virale</term>
<term>Séquence d'acides aminés</term>
</keywords>
<keywords scheme="MESH" type="chemical" qualifier="antagonists & inhibitors" xml:lang="en"><term>Viral Fusion Proteins</term>
</keywords>
<keywords scheme="MESH" type="chemical" qualifier="chemistry" xml:lang="en"><term>Peptides</term>
<term>Spike Glycoprotein, Coronavirus</term>
<term>Viral Proteins</term>
</keywords>
<keywords scheme="MESH" qualifier="antagonistes et inhibiteurs" xml:lang="fr"><term>Protéines de fusion virale</term>
</keywords>
<keywords scheme="MESH" qualifier="metabolism" xml:lang="en"><term>Middle East Respiratory Syndrome Coronavirus</term>
<term>Peptides</term>
<term>Spike Glycoprotein, Coronavirus</term>
<term>Viral Fusion Proteins</term>
<term>Viral Proteins</term>
</keywords>
<keywords scheme="MESH" qualifier="métabolisme" xml:lang="fr"><term>Coronavirus du syndrome respiratoire du Moyen-Orient</term>
<term>Glycoprotéine de spicule des coronavirus</term>
<term>Peptides</term>
<term>Protéines de fusion virale</term>
<term>Protéines virales</term>
</keywords>
<keywords scheme="MESH" xml:lang="en"><term>Amino Acid Sequence</term>
<term>Crystallography, X-Ray</term>
<term>Humans</term>
<term>Molecular Sequence Data</term>
<term>Virus Internalization</term>
<term>Virus Replication</term>
</keywords>
<keywords scheme="MESH" xml:lang="fr"><term>Cristallographie aux rayons X</term>
<term>Données de séquences moléculaires</term>
<term>Glycoprotéine de spicule des coronavirus</term>
<term>Humains</term>
<term>Peptides</term>
<term>Protéines virales</term>
<term>Pénétration virale</term>
<term>Réplication virale</term>
<term>Séquence d'acides aminés</term>
</keywords>
</textClass>
</profileDesc>
</teiHeader>
<front><div type="abstract" xml:lang="en">A novel human coronavirus, Middle East respiratory syndrome coronavirus (MERS-CoV), has caused outbreaks of a SARS-like illness with high case fatality rate. The reports of its person-to-person transmission through close contacts have raised a global concern about its pandemic potential. Here we characterize the six-helix bundle fusion core structure of MERS-CoV spike protein S2 subunit by X-ray crystallography and biophysical analysis. We find that two peptides, HR1P and HR2P, spanning residues 998-1039 in HR1 and 1251-1286 in HR2 domains, respectively, can form a stable six-helix bundle fusion core structure, suggesting that MERS-CoV enters into the host cell mainly through membrane fusion mechanism. HR2P can effectively inhibit MERS-CoV replication and its spike protein-mediated cell-cell fusion. Introduction of hydrophilic residues into HR2P results in significant improvement of its stability, solubility and antiviral activity. Therefore, the HR2P analogues have good potential to be further developed into effective viral fusion inhibitors for treating MERS-CoV infection. </div>
</front>
</TEI>
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