Serveur d'exploration MERS

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A conformation-dependent neutralizing monoclonal antibody specifically targeting receptor-binding domain in Middle East respiratory syndrome coronavirus spike protein.

Identifieur interne : 001D61 ( Main/Exploration ); précédent : 001D60; suivant : 001D62

A conformation-dependent neutralizing monoclonal antibody specifically targeting receptor-binding domain in Middle East respiratory syndrome coronavirus spike protein.

Auteurs : Lanying Du [États-Unis] ; Guangyu Zhao [République populaire de Chine] ; Yang Yang [États-Unis] ; Hongjie Qiu [République populaire de Chine] ; Lili Wang [États-Unis] ; Zhihua Kou [République populaire de Chine] ; Xinrong Tao [États-Unis] ; Hong Yu [République populaire de Chine] ; Shihui Sun [République populaire de Chine] ; Chien-Te K. Tseng [États-Unis] ; Shibo Jiang [République populaire de Chine] ; Fang Li [États-Unis] ; Yusen Zhou [États-Unis]

Source :

RBID : pubmed:24719424

Descripteurs français

English descriptors

Abstract

Prophylactic and therapeutic strategies are urgently needed to combat infections caused by the newly emerged Middle East respiratory syndrome coronavirus (MERS-CoV). Here, we have developed a neutralizing monoclonal antibody (MAb), designated Mersmab1, which potently blocks MERS-CoV entry into human cells. Biochemical assays reveal that Mersmab1 specifically binds to the receptor-binding domain (RBD) of the MERS-CoV spike protein and thereby competitively blocks the binding of the RBD to its cellular receptor, dipeptidyl peptidase 4 (DPP4). Furthermore, alanine scanning of the RBD has identified several residues at the DPP4-binding surface that serve as neutralizing epitopes for Mersmab1. These results suggest that if humanized, Mersmab1 could potentially function as a therapeutic antibody for treating and preventing MERS-CoV infections. Additionally, Mersmab1 may facilitate studies of the conformation and antigenicity of MERS-CoV RBD and thus will guide rational design of MERS-CoV subunit vaccines.

DOI: 10.1128/JVI.00433-14
PubMed: 24719424


Affiliations:


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Le document en format XML

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<name sortKey="Yu, Hong" sort="Yu, Hong" uniqKey="Yu H" first="Hong" last="Yu">Hong Yu</name>
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</keywords>
<keywords scheme="MESH" qualifier="genetics" xml:lang="en">
<term>Coronaviridae</term>
<term>Coronaviridae Infections</term>
</keywords>
<keywords scheme="MESH" qualifier="génétique" xml:lang="fr">
<term>Coronaviridae</term>
<term>Dipeptidyl peptidase 4</term>
<term>Glycoprotéine de spicule des coronavirus</term>
<term>Infections à Coronaviridae</term>
<term>Récepteurs viraux</term>
</keywords>
<keywords scheme="MESH" qualifier="métabolisme" xml:lang="fr">
<term>Dipeptidyl peptidase 4</term>
<term>Glycoprotéine de spicule des coronavirus</term>
<term>Récepteurs viraux</term>
</keywords>
<keywords scheme="MESH" qualifier="pharmacologie" xml:lang="fr">
<term>Anticorps antiviraux</term>
<term>Anticorps neutralisants</term>
</keywords>
<keywords scheme="MESH" qualifier="physiologie" xml:lang="fr">
<term>Coronaviridae</term>
</keywords>
<keywords scheme="MESH" qualifier="physiology" xml:lang="en">
<term>Coronaviridae</term>
</keywords>
<keywords scheme="MESH" qualifier="virologie" xml:lang="fr">
<term>Infections à Coronaviridae</term>
</keywords>
<keywords scheme="MESH" qualifier="virology" xml:lang="en">
<term>Coronaviridae Infections</term>
</keywords>
<keywords scheme="MESH" xml:lang="en">
<term>Animals</term>
<term>Epitope Mapping</term>
<term>Female</term>
<term>Humans</term>
<term>Mice</term>
<term>Mice, Inbred BALB C</term>
<term>Protein Binding</term>
<term>Protein Structure, Tertiary</term>
</keywords>
<keywords scheme="MESH" xml:lang="fr">
<term>Animaux</term>
<term>Anticorps antiviraux</term>
<term>Anticorps neutralisants</term>
<term>Cartographie épitopique</term>
<term>Coronaviridae</term>
<term>Femelle</term>
<term>Glycoprotéine de spicule des coronavirus</term>
<term>Humains</term>
<term>Liaison aux protéines</term>
<term>Pénétration virale</term>
<term>Souris</term>
<term>Souris de lignée BALB C</term>
<term>Structure tertiaire des protéines</term>
</keywords>
</textClass>
</profileDesc>
</teiHeader>
<front>
<div type="abstract" xml:lang="en">Prophylactic and therapeutic strategies are urgently needed to combat infections caused by the newly emerged Middle East respiratory syndrome coronavirus (MERS-CoV). Here, we have developed a neutralizing monoclonal antibody (MAb), designated Mersmab1, which potently blocks MERS-CoV entry into human cells. Biochemical assays reveal that Mersmab1 specifically binds to the receptor-binding domain (RBD) of the MERS-CoV spike protein and thereby competitively blocks the binding of the RBD to its cellular receptor, dipeptidyl peptidase 4 (DPP4). Furthermore, alanine scanning of the RBD has identified several residues at the DPP4-binding surface that serve as neutralizing epitopes for Mersmab1. These results suggest that if humanized, Mersmab1 could potentially function as a therapeutic antibody for treating and preventing MERS-CoV infections. Additionally, Mersmab1 may facilitate studies of the conformation and antigenicity of MERS-CoV RBD and thus will guide rational design of MERS-CoV subunit vaccines.</div>
</front>
</TEI>
<affiliations>
<list>
<country>
<li>République populaire de Chine</li>
<li>États-Unis</li>
</country>
<region>
<li>Minnesota</li>
<li>Texas</li>
<li>État de New York</li>
</region>
<settlement>
<li>Pékin</li>
</settlement>
</list>
<tree>
<country name="États-Unis">
<region name="État de New York">
<name sortKey="Du, Lanying" sort="Du, Lanying" uniqKey="Du L" first="Lanying" last="Du">Lanying Du</name>
</region>
<name sortKey="Li, Fang" sort="Li, Fang" uniqKey="Li F" first="Fang" last="Li">Fang Li</name>
<name sortKey="Tao, Xinrong" sort="Tao, Xinrong" uniqKey="Tao X" first="Xinrong" last="Tao">Xinrong Tao</name>
<name sortKey="Tseng, Chien Te K" sort="Tseng, Chien Te K" uniqKey="Tseng C" first="Chien-Te K" last="Tseng">Chien-Te K. Tseng</name>
<name sortKey="Wang, Lili" sort="Wang, Lili" uniqKey="Wang L" first="Lili" last="Wang">Lili Wang</name>
<name sortKey="Yang, Yang" sort="Yang, Yang" uniqKey="Yang Y" first="Yang" last="Yang">Yang Yang</name>
<name sortKey="Zhou, Yusen" sort="Zhou, Yusen" uniqKey="Zhou Y" first="Yusen" last="Zhou">Yusen Zhou</name>
</country>
<country name="République populaire de Chine">
<noRegion>
<name sortKey="Zhao, Guangyu" sort="Zhao, Guangyu" uniqKey="Zhao G" first="Guangyu" last="Zhao">Guangyu Zhao</name>
</noRegion>
<name sortKey="Jiang, Shibo" sort="Jiang, Shibo" uniqKey="Jiang S" first="Shibo" last="Jiang">Shibo Jiang</name>
<name sortKey="Kou, Zhihua" sort="Kou, Zhihua" uniqKey="Kou Z" first="Zhihua" last="Kou">Zhihua Kou</name>
<name sortKey="Qiu, Hongjie" sort="Qiu, Hongjie" uniqKey="Qiu H" first="Hongjie" last="Qiu">Hongjie Qiu</name>
<name sortKey="Sun, Shihui" sort="Sun, Shihui" uniqKey="Sun S" first="Shihui" last="Sun">Shihui Sun</name>
<name sortKey="Yu, Hong" sort="Yu, Hong" uniqKey="Yu H" first="Hong" last="Yu">Hong Yu</name>
</country>
</tree>
</affiliations>
</record>

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