Conserved amino acids W423 and N424 in receptor-binding domain of SARS-CoV are potential targets for therapeutic monoclonal antibody.
Identifieur interne : 002B57 ( Main/Exploration ); précédent : 002B56; suivant : 002B58Conserved amino acids W423 and N424 in receptor-binding domain of SARS-CoV are potential targets for therapeutic monoclonal antibody.
Auteurs : Chao Bian [République populaire de Chine] ; Xiuqin Zhang ; Xingfeng Cai ; Linqi Zhang ; Zhiwei Chen ; Ye Zha ; Ying Xu ; Ke Xu ; Wei Lu ; Linchen Yan ; Jianwei Yuan ; Jiannan Feng ; Pei Hao ; Qidi Wang ; Guoping Zhao ; Gang Liu ; Xueliang Zhu ; Hao Shen ; Bojian Zheng ; Beifen Shen ; Bing SunSource :
- Virology [ 1096-0341 ] ; 2009.
Descripteurs français
- KwdFr :
- Animaux, Anticorps antiviraux (immunologie), Anticorps antiviraux (isolement et purification), Anticorps antiviraux (usage thérapeutique), Anticorps monoclonaux (immunologie), Anticorps monoclonaux (isolement et purification), Anticorps monoclonaux (usage thérapeutique), Attachement viral, Données de séquences moléculaires, Femelle, Glycoprotéine de spicule des coronavirus, Glycoprotéines membranaires (), Glycoprotéines membranaires (antagonistes et inhibiteurs), Glycoprotéines membranaires (immunologie), Humains, Modèles moléculaires, Protéines de l'enveloppe virale (), Protéines de l'enveloppe virale (antagonistes et inhibiteurs), Protéines de l'enveloppe virale (immunologie), Souris, Souris de lignée BALB C, Structure tertiaire des protéines, Séquence conservée (immunologie), Séquence d'acides aminés, Tests de neutralisation, Virus du SRAS (immunologie), Virus du SRAS (physiologie), Épitopes (immunologie).
- MESH :
- antagonistes et inhibiteurs : Glycoprotéines membranaires, Protéines de l'enveloppe virale.
- immunologie : Anticorps antiviraux, Anticorps monoclonaux, Glycoprotéines membranaires, Protéines de l'enveloppe virale, Séquence conservée, Virus du SRAS, Épitopes.
- isolement et purification : Anticorps antiviraux, Anticorps monoclonaux.
- physiologie : Virus du SRAS.
- usage thérapeutique : Anticorps antiviraux, Anticorps monoclonaux.
- Animaux, Attachement viral, Données de séquences moléculaires, Femelle, Glycoprotéine de spicule des coronavirus, Glycoprotéines membranaires, Humains, Modèles moléculaires, Protéines de l'enveloppe virale, Souris, Souris de lignée BALB C, Structure tertiaire des protéines, Séquence d'acides aminés, Tests de neutralisation.
English descriptors
- KwdEn :
- Amino Acid Sequence, Animals, Antibodies, Monoclonal (immunology), Antibodies, Monoclonal (isolation & purification), Antibodies, Monoclonal (therapeutic use), Antibodies, Viral (immunology), Antibodies, Viral (isolation & purification), Antibodies, Viral (therapeutic use), Conserved Sequence (immunology), Epitopes (immunology), Female, Humans, Membrane Glycoproteins (antagonists & inhibitors), Membrane Glycoproteins (chemistry), Membrane Glycoproteins (immunology), Mice, Mice, Inbred BALB C, Models, Molecular, Molecular Sequence Data, Neutralization Tests, Protein Structure, Tertiary, SARS Virus (immunology), SARS Virus (physiology), Spike Glycoprotein, Coronavirus, Viral Envelope Proteins (antagonists & inhibitors), Viral Envelope Proteins (chemistry), Viral Envelope Proteins (immunology), Virus Attachment.
- MESH :
- chemical , antagonists & inhibitors : Membrane Glycoproteins, Viral Envelope Proteins.
- chemical , chemistry : Membrane Glycoproteins, Viral Envelope Proteins.
- chemical , immunology : Antibodies, Monoclonal, Antibodies, Viral, Epitopes, Membrane Glycoproteins, Viral Envelope Proteins.
- chemical , isolation & purification : Antibodies, Monoclonal, Antibodies, Viral.
- chemical , therapeutic use : Antibodies, Monoclonal, Antibodies, Viral.
- immunology : Conserved Sequence, SARS Virus.
- physiology : SARS Virus.
- Amino Acid Sequence, Animals, Female, Humans, Mice, Mice, Inbred BALB C, Models, Molecular, Molecular Sequence Data, Neutralization Tests, Protein Structure, Tertiary, Spike Glycoprotein, Coronavirus, Virus Attachment.
Abstract
The receptor-binding domain (RBD) on spike protein of severe acute respiratory syndrome-associated coronavirus (SARS-CoV) is the main region interacting with the viral receptor-ACE2 and is a useful target for induction of neutralizing antibodies against SARS-CoV infection. Here we generated two monoclonal antibodies (mAbs), targeting RBD, with marked virus neutralizing activity. The mAbs recognize a new conformational epitope which consists of several discontinuous peptides (aa. 343-367, 373-390 and 411-428) and is spatially located neighboring the receptor-binding motif (RPM) region of the RBD. Importantly, W423 and N424 residues are essential for mAb recognition and are highly conserved among 107 different strains of SARS, indicating that the residues are the most critical in the epitope which is a novel potential target for therapeutic mAbs. A human-mouse chimeric antibody, based upon the original murine mAb, was also constructed and shown to possess good neutralizing activity and high affinity.
DOI: 10.1016/j.virol.2008.09.029
PubMed: 18986662
Affiliations:
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Le document en format XML
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uniqKey="Zhang X" first="Xiuqin" last="Zhang">Xiuqin Zhang</name></author><author><name sortKey="Cai, Xingfeng" sort="Cai, Xingfeng" uniqKey="Cai X" first="Xingfeng" last="Cai">Xingfeng Cai</name></author><author><name sortKey="Zhang, Linqi" sort="Zhang, Linqi" uniqKey="Zhang L" first="Linqi" last="Zhang">Linqi Zhang</name></author><author><name sortKey="Chen, Zhiwei" sort="Chen, Zhiwei" uniqKey="Chen Z" first="Zhiwei" last="Chen">Zhiwei Chen</name></author><author><name sortKey="Zha, Ye" sort="Zha, Ye" uniqKey="Zha Y" first="Ye" last="Zha">Ye Zha</name></author><author><name sortKey="Xu, Ying" sort="Xu, Ying" uniqKey="Xu Y" first="Ying" last="Xu">Ying Xu</name></author><author><name sortKey="Xu, Ke" sort="Xu, Ke" uniqKey="Xu K" first="Ke" last="Xu">Ke Xu</name></author><author><name sortKey="Lu, Wei" sort="Lu, Wei" uniqKey="Lu W" first="Wei" last="Lu">Wei Lu</name></author><author><name sortKey="Yan, Linchen" sort="Yan, Linchen" uniqKey="Yan L" first="Linchen" last="Yan">Linchen 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Chine</country><wicri:regionArea>Laboratory of Molecular Cell Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, 320 Yueyang Road, Shanghai 200031</wicri:regionArea><wicri:noRegion>Shanghai 200031</wicri:noRegion></affiliation></author><author><name sortKey="Zhang, Xiuqin" sort="Zhang, Xiuqin" uniqKey="Zhang X" first="Xiuqin" last="Zhang">Xiuqin Zhang</name></author><author><name sortKey="Cai, Xingfeng" sort="Cai, Xingfeng" uniqKey="Cai X" first="Xingfeng" last="Cai">Xingfeng Cai</name></author><author><name sortKey="Zhang, Linqi" sort="Zhang, Linqi" uniqKey="Zhang L" first="Linqi" last="Zhang">Linqi Zhang</name></author><author><name sortKey="Chen, Zhiwei" sort="Chen, Zhiwei" uniqKey="Chen Z" first="Zhiwei" last="Chen">Zhiwei Chen</name></author><author><name sortKey="Zha, Ye" sort="Zha, Ye" uniqKey="Zha Y" first="Ye" last="Zha">Ye Zha</name></author><author><name sortKey="Xu, Ying" sort="Xu, Ying" uniqKey="Xu Y" first="Ying" last="Xu">Ying Xu</name></author><author><name sortKey="Xu, Ke" sort="Xu, Ke" uniqKey="Xu K" first="Ke" last="Xu">Ke Xu</name></author><author><name sortKey="Lu, Wei" sort="Lu, Wei" uniqKey="Lu W" first="Wei" last="Lu">Wei Lu</name></author><author><name sortKey="Yan, Linchen" sort="Yan, Linchen" uniqKey="Yan L" first="Linchen" last="Yan">Linchen Yan</name></author><author><name sortKey="Yuan, Jianwei" sort="Yuan, Jianwei" uniqKey="Yuan J" first="Jianwei" last="Yuan">Jianwei Yuan</name></author><author><name sortKey="Feng, Jiannan" sort="Feng, Jiannan" uniqKey="Feng J" first="Jiannan" last="Feng">Jiannan Feng</name></author><author><name sortKey="Hao, Pei" sort="Hao, Pei" uniqKey="Hao P" first="Pei" last="Hao">Pei Hao</name></author><author><name sortKey="Wang, Qidi" sort="Wang, Qidi" uniqKey="Wang Q" first="Qidi" last="Wang">Qidi Wang</name></author><author><name sortKey="Zhao, Guoping" sort="Zhao, Guoping" uniqKey="Zhao G" first="Guoping" last="Zhao">Guoping Zhao</name></author><author><name sortKey="Liu, Gang" sort="Liu, Gang" uniqKey="Liu G" first="Gang" last="Liu">Gang Liu</name></author><author><name sortKey="Zhu, Xueliang" sort="Zhu, Xueliang" uniqKey="Zhu X" first="Xueliang" last="Zhu">Xueliang Zhu</name></author><author><name sortKey="Shen, Hao" sort="Shen, Hao" uniqKey="Shen H" first="Hao" last="Shen">Hao Shen</name></author><author><name sortKey="Zheng, Bojian" sort="Zheng, Bojian" uniqKey="Zheng B" first="Bojian" last="Zheng">Bojian Zheng</name></author><author><name sortKey="Shen, Beifen" sort="Shen, Beifen" uniqKey="Shen B" first="Beifen" last="Shen">Beifen Shen</name></author><author><name sortKey="Sun, Bing" sort="Sun, Bing" uniqKey="Sun B" first="Bing" last="Sun">Bing Sun</name></author></analytic><series><title level="j">Virology</title><idno type="eISSN">1096-0341</idno><imprint><date when="2009" type="published">2009</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Amino Acid Sequence</term><term>Animals</term><term>Antibodies, Monoclonal (immunology)</term><term>Antibodies, Monoclonal (isolation & purification)</term><term>Antibodies, Monoclonal (therapeutic use)</term><term>Antibodies, Viral (immunology)</term><term>Antibodies, Viral (isolation & purification)</term><term>Antibodies, Viral (therapeutic use)</term><term>Conserved Sequence (immunology)</term><term>Epitopes (immunology)</term><term>Female</term><term>Humans</term><term>Membrane Glycoproteins (antagonists & inhibitors)</term><term>Membrane Glycoproteins (chemistry)</term><term>Membrane Glycoproteins (immunology)</term><term>Mice</term><term>Mice, Inbred BALB C</term><term>Models, Molecular</term><term>Molecular Sequence Data</term><term>Neutralization Tests</term><term>Protein Structure, Tertiary</term><term>SARS Virus (immunology)</term><term>SARS Virus (physiology)</term><term>Spike Glycoprotein, Coronavirus</term><term>Viral Envelope Proteins (antagonists & inhibitors)</term><term>Viral Envelope Proteins (chemistry)</term><term>Viral Envelope Proteins (immunology)</term><term>Virus Attachment</term></keywords><keywords scheme="KwdFr" xml:lang="fr"><term>Animaux</term><term>Anticorps antiviraux (immunologie)</term><term>Anticorps antiviraux (isolement et purification)</term><term>Anticorps antiviraux (usage thérapeutique)</term><term>Anticorps monoclonaux (immunologie)</term><term>Anticorps monoclonaux (isolement et purification)</term><term>Anticorps monoclonaux (usage thérapeutique)</term><term>Attachement viral</term><term>Données de séquences moléculaires</term><term>Femelle</term><term>Glycoprotéine de spicule des coronavirus</term><term>Glycoprotéines membranaires ()</term><term>Glycoprotéines membranaires (antagonistes et inhibiteurs)</term><term>Glycoprotéines membranaires (immunologie)</term><term>Humains</term><term>Modèles moléculaires</term><term>Protéines de l'enveloppe virale ()</term><term>Protéines de l'enveloppe virale (antagonistes et inhibiteurs)</term><term>Protéines de l'enveloppe virale (immunologie)</term><term>Souris</term><term>Souris de lignée BALB C</term><term>Structure tertiaire des protéines</term><term>Séquence conservée (immunologie)</term><term>Séquence d'acides aminés</term><term>Tests de neutralisation</term><term>Virus du SRAS (immunologie)</term><term>Virus du SRAS (physiologie)</term><term>Épitopes (immunologie)</term></keywords><keywords scheme="MESH" type="chemical" qualifier="antagonists & inhibitors" xml:lang="en"><term>Membrane Glycoproteins</term><term>Viral Envelope Proteins</term></keywords><keywords scheme="MESH" type="chemical" qualifier="chemistry" xml:lang="en"><term>Membrane Glycoproteins</term><term>Viral Envelope Proteins</term></keywords><keywords scheme="MESH" type="chemical" qualifier="immunology" xml:lang="en"><term>Antibodies, Monoclonal</term><term>Antibodies, Viral</term><term>Epitopes</term><term>Membrane Glycoproteins</term><term>Viral Envelope Proteins</term></keywords><keywords scheme="MESH" type="chemical" qualifier="isolation & purification" xml:lang="en"><term>Antibodies, Monoclonal</term><term>Antibodies, Viral</term></keywords><keywords scheme="MESH" type="chemical" qualifier="therapeutic use" xml:lang="en"><term>Antibodies, Monoclonal</term><term>Antibodies, Viral</term></keywords><keywords scheme="MESH" qualifier="antagonistes et inhibiteurs" xml:lang="fr"><term>Glycoprotéines membranaires</term><term>Protéines de l'enveloppe virale</term></keywords><keywords scheme="MESH" qualifier="immunologie" xml:lang="fr"><term>Anticorps antiviraux</term><term>Anticorps monoclonaux</term><term>Glycoprotéines membranaires</term><term>Protéines de l'enveloppe virale</term><term>Séquence conservée</term><term>Virus du SRAS</term><term>Épitopes</term></keywords><keywords scheme="MESH" qualifier="immunology" xml:lang="en"><term>Conserved Sequence</term><term>SARS Virus</term></keywords><keywords scheme="MESH" qualifier="isolement et purification" xml:lang="fr"><term>Anticorps antiviraux</term><term>Anticorps monoclonaux</term></keywords><keywords scheme="MESH" qualifier="physiologie" xml:lang="fr"><term>Virus du SRAS</term></keywords><keywords scheme="MESH" qualifier="physiology" xml:lang="en"><term>SARS Virus</term></keywords><keywords scheme="MESH" qualifier="usage thérapeutique" xml:lang="fr"><term>Anticorps antiviraux</term><term>Anticorps monoclonaux</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Amino Acid Sequence</term><term>Animals</term><term>Female</term><term>Humans</term><term>Mice</term><term>Mice, Inbred BALB C</term><term>Models, Molecular</term><term>Molecular Sequence Data</term><term>Neutralization Tests</term><term>Protein Structure, Tertiary</term><term>Spike Glycoprotein, Coronavirus</term><term>Virus Attachment</term></keywords><keywords scheme="MESH" xml:lang="fr"><term>Animaux</term><term>Attachement viral</term><term>Données de séquences moléculaires</term><term>Femelle</term><term>Glycoprotéine de spicule des coronavirus</term><term>Glycoprotéines membranaires</term><term>Humains</term><term>Modèles moléculaires</term><term>Protéines de l'enveloppe virale</term><term>Souris</term><term>Souris de lignée BALB C</term><term>Structure tertiaire des protéines</term><term>Séquence d'acides aminés</term><term>Tests de neutralisation</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">The receptor-binding domain (RBD) on spike protein of severe acute respiratory syndrome-associated coronavirus (SARS-CoV) is the main region interacting with the viral receptor-ACE2 and is a useful target for induction of neutralizing antibodies against SARS-CoV infection. Here we generated two monoclonal antibodies (mAbs), targeting RBD, with marked virus neutralizing activity. The mAbs recognize a new conformational epitope which consists of several discontinuous peptides (aa. 343-367, 373-390 and 411-428) and is spatially located neighboring the receptor-binding motif (RPM) region of the RBD. Importantly, W423 and N424 residues are essential for mAb recognition and are highly conserved among 107 different strains of SARS, indicating that the residues are the most critical in the epitope which is a novel potential target for therapeutic mAbs. A human-mouse chimeric antibody, based upon the original murine mAb, was also constructed and shown to possess good neutralizing activity and high affinity.</div></front></TEI><affiliations><list><country><li>République populaire de Chine</li></country></list><tree><noCountry><name sortKey="Cai, Xingfeng" sort="Cai, Xingfeng" uniqKey="Cai X" first="Xingfeng" last="Cai">Xingfeng Cai</name><name sortKey="Chen, Zhiwei" sort="Chen, Zhiwei" uniqKey="Chen Z" first="Zhiwei" last="Chen">Zhiwei Chen</name><name sortKey="Feng, Jiannan" sort="Feng, Jiannan" uniqKey="Feng J" first="Jiannan" last="Feng">Jiannan Feng</name><name sortKey="Hao, Pei" sort="Hao, Pei" uniqKey="Hao P" first="Pei" last="Hao">Pei Hao</name><name sortKey="Liu, Gang" sort="Liu, Gang" uniqKey="Liu G" first="Gang" last="Liu">Gang Liu</name><name sortKey="Lu, Wei" sort="Lu, Wei" uniqKey="Lu W" first="Wei" last="Lu">Wei Lu</name><name sortKey="Shen, Beifen" sort="Shen, Beifen" uniqKey="Shen B" first="Beifen" last="Shen">Beifen Shen</name><name sortKey="Shen, Hao" sort="Shen, Hao" uniqKey="Shen H" first="Hao" last="Shen">Hao Shen</name><name sortKey="Sun, Bing" sort="Sun, Bing" uniqKey="Sun B" first="Bing" last="Sun">Bing Sun</name><name sortKey="Wang, Qidi" sort="Wang, Qidi" uniqKey="Wang Q" first="Qidi" last="Wang">Qidi Wang</name><name sortKey="Xu, Ke" sort="Xu, Ke" uniqKey="Xu K" first="Ke" last="Xu">Ke Xu</name><name sortKey="Xu, Ying" sort="Xu, Ying" uniqKey="Xu Y" first="Ying" last="Xu">Ying Xu</name><name sortKey="Yan, Linchen" sort="Yan, Linchen" uniqKey="Yan L" first="Linchen" last="Yan">Linchen Yan</name><name sortKey="Yuan, Jianwei" sort="Yuan, Jianwei" uniqKey="Yuan J" first="Jianwei" last="Yuan">Jianwei Yuan</name><name sortKey="Zha, Ye" sort="Zha, Ye" uniqKey="Zha Y" first="Ye" last="Zha">Ye Zha</name><name sortKey="Zhang, Linqi" sort="Zhang, Linqi" uniqKey="Zhang L" first="Linqi" last="Zhang">Linqi Zhang</name><name sortKey="Zhang, Xiuqin" sort="Zhang, Xiuqin" uniqKey="Zhang X" first="Xiuqin" last="Zhang">Xiuqin Zhang</name><name sortKey="Zhao, Guoping" sort="Zhao, Guoping" uniqKey="Zhao G" first="Guoping" last="Zhao">Guoping Zhao</name><name sortKey="Zheng, Bojian" sort="Zheng, Bojian" uniqKey="Zheng B" first="Bojian" last="Zheng">Bojian Zheng</name><name sortKey="Zhu, Xueliang" sort="Zhu, Xueliang" uniqKey="Zhu X" first="Xueliang" last="Zhu">Xueliang Zhu</name></noCountry><country name="République populaire de Chine"><noRegion><name sortKey="Bian, Chao" sort="Bian, Chao" uniqKey="Bian C" first="Chao" last="Bian">Chao Bian</name></noRegion></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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