Combining a Fusion Inhibitory Peptide Targeting the MERS-CoV S2 Protein HR1 Domain and a Neutralizing Antibody Specific for the S1 Protein Receptor-Binding Domain (RBD) Showed Potent Synergism against Pseudotyped MERS-CoV with or without Mutations in RBD
Identifieur interne : 000659 ( Main/Exploration ); précédent : 000658; suivant : 000660Combining a Fusion Inhibitory Peptide Targeting the MERS-CoV S2 Protein HR1 Domain and a Neutralizing Antibody Specific for the S1 Protein Receptor-Binding Domain (RBD) Showed Potent Synergism against Pseudotyped MERS-CoV with or without Mutations in RBD
Auteurs : Cong Wang ; Chen Hua ; Shuai Xia ; Weihua Li ; Lu Lu ; Shibo JiangSource :
- Viruses [ 1999-4915 ] ; 2019.
Descripteurs français
- KwdFr :
- Animaux, Anticorps antiviraux (immunologie), Anticorps neutralisants (immunologie), Cellules HEK293, Coronavirus du syndrome respiratoire du Moyen-Orient (génétique), Domaines protéiques, Femelle, Glycoprotéine de spicule des coronavirus (génétique), Glycoprotéine de spicule des coronavirus (immunologie), Humains, Liaison aux protéines, Mutation, Peptides (génétique), Peptides (immunologie), Pénétration virale, Souris, Souris de lignée BALB C, Synergie des médicaments.
- MESH :
- génétique : Coronavirus du syndrome respiratoire du Moyen-Orient, Glycoprotéine de spicule des coronavirus, Peptides.
- immunologie : Anticorps antiviraux, Anticorps neutralisants, Glycoprotéine de spicule des coronavirus, Peptides.
- Animaux, Cellules HEK293, Domaines protéiques, Femelle, Humains, Liaison aux protéines, Mutation, Pénétration virale, Souris, Souris de lignée BALB C, Synergie des médicaments.
English descriptors
- KwdEn :
- Animals, Antibodies, Neutralizing (immunology), Antibodies, Viral (immunology), Drug Synergism, Female, HEK293 Cells, Humans, Mice, Mice, Inbred BALB C, Middle East Respiratory Syndrome Coronavirus (genetics), Mutation, Peptides (genetics), Peptides (immunology), Protein Binding, Protein Domains, Spike Glycoprotein, Coronavirus (genetics), Spike Glycoprotein, Coronavirus (immunology), Virus Internalization.
- MESH :
- chemical , genetics : Peptides, Spike Glycoprotein, Coronavirus.
- chemical , immunology : Antibodies, Neutralizing, Antibodies, Viral, Peptides, Spike Glycoprotein, Coronavirus.
- genetics : Middle East Respiratory Syndrome Coronavirus.
- Animals, Drug Synergism, Female, HEK293 Cells, Humans, Mice, Mice, Inbred BALB C, Mutation, Protein Binding, Protein Domains, Virus Internalization.
Abstract
Middle East respiratory syndrome coronavirus (MERS-CoV) has continuously posed a threat to public health worldwide, yet no therapeutics or vaccines are currently available to prevent or treat MERS-CoV infection. We previously identified a fusion inhibitory peptide (HR2P-M2) targeting the MERS-CoV S2 protein HR1 domain and a highly potent neutralizing monoclonal antibody (m336) specific to the S1 spike protein receptor-binding domain (RBD). However, m336 was found to have reduced efficacy against MERS-CoV strains with mutations in RBD, and HR2P-M2 showed low potency, thus limiting the clinical application of each when administered separately. However, we herein report that the combination of m336 and HR2P-M2 exhibited potent synergism in inhibiting MERS-CoV S protein-mediated cell–cell fusion and infection by MERS-CoV pseudoviruses with or without mutations in the RBD, resulting in the enhancement of antiviral activity in contrast to either one administered alone. Thus, this combinatorial strategy could be used in clinics for the urgent treatment of MERS-CoV-infected patients.
Url:
DOI: 10.3390/v11010031
PubMed: 30621343
PubMed Central: 6356712
Affiliations:
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Le document en format XML
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Laboratory of Medical Molecular Virology of MOE/MOH, School of Basic Medical Sciences and Shanghai Public Health Clinical Center, Fudan University, Shanghai 200032, China;<email>16111010068@fudan.edu.cn</email> (C.W.);<email>16211010047@fudan.edu.cn</email> (C.H.);<email>15111010053@fudan.edu.cn</email> (S.X.)</nlm:aff></affiliation></author><author><name sortKey="Xia, Shuai" sort="Xia, Shuai" uniqKey="Xia S" first="Shuai" last="Xia">Shuai Xia</name><affiliation><nlm:aff id="af1-viruses-11-00031">Key Laboratory of Medical Molecular Virology of MOE/MOH, School of Basic Medical Sciences and Shanghai Public Health Clinical Center, Fudan University, Shanghai 200032, China;<email>16111010068@fudan.edu.cn</email> (C.W.);<email>16211010047@fudan.edu.cn</email> (C.H.);<email>15111010053@fudan.edu.cn</email> (S.X.)</nlm:aff></affiliation></author><author><name sortKey="Li, Weihua" sort="Li, Weihua" uniqKey="Li W" first="Weihua" last="Li">Weihua Li</name><affiliation><nlm:aff id="af2-viruses-11-00031">NHC Key Laboratory of Reproduction Regulation (Shanghai Institute of Planned Parenthood Research), Fudan University, Shanghai 200032, China;<email>weihua.li@sippr.org.cn</email></nlm:aff></affiliation></author><author><name sortKey="Lu, Lu" sort="Lu, Lu" uniqKey="Lu L" first="Lu" last="Lu">Lu Lu</name><affiliation><nlm:aff id="af1-viruses-11-00031">Key Laboratory of Medical Molecular Virology of MOE/MOH, School of Basic Medical Sciences and Shanghai Public Health Clinical Center, Fudan University, Shanghai 200032, China;<email>16111010068@fudan.edu.cn</email> (C.W.);<email>16211010047@fudan.edu.cn</email> (C.H.);<email>15111010053@fudan.edu.cn</email> (S.X.)</nlm:aff></affiliation></author><author><name sortKey="Jiang, Shibo" sort="Jiang, Shibo" uniqKey="Jiang S" first="Shibo" last="Jiang">Shibo Jiang</name><affiliation><nlm:aff id="af1-viruses-11-00031">Key Laboratory of Medical Molecular Virology of MOE/MOH, School of Basic Medical Sciences and Shanghai 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sort="Hua, Chen" uniqKey="Hua C" first="Chen" last="Hua">Chen Hua</name><affiliation><nlm:aff id="af1-viruses-11-00031">Key Laboratory of Medical Molecular Virology of MOE/MOH, School of Basic Medical Sciences and Shanghai Public Health Clinical Center, Fudan University, Shanghai 200032, China;<email>16111010068@fudan.edu.cn</email> (C.W.);<email>16211010047@fudan.edu.cn</email> (C.H.);<email>15111010053@fudan.edu.cn</email> (S.X.)</nlm:aff></affiliation></author><author><name sortKey="Xia, Shuai" sort="Xia, Shuai" uniqKey="Xia S" first="Shuai" last="Xia">Shuai Xia</name><affiliation><nlm:aff id="af1-viruses-11-00031">Key Laboratory of Medical Molecular Virology of MOE/MOH, School of Basic Medical Sciences and Shanghai Public Health Clinical Center, Fudan University, Shanghai 200032, China;<email>16111010068@fudan.edu.cn</email> (C.W.);<email>16211010047@fudan.edu.cn</email> (C.H.);<email>15111010053@fudan.edu.cn</email> (S.X.)</nlm:aff></affiliation></author><author><name sortKey="Li, Weihua" sort="Li, Weihua" uniqKey="Li W" first="Weihua" last="Li">Weihua Li</name><affiliation><nlm:aff id="af2-viruses-11-00031">NHC Key Laboratory of Reproduction Regulation (Shanghai Institute of Planned Parenthood Research), Fudan University, Shanghai 200032, China;<email>weihua.li@sippr.org.cn</email></nlm:aff></affiliation></author><author><name sortKey="Lu, Lu" sort="Lu, Lu" uniqKey="Lu L" first="Lu" last="Lu">Lu Lu</name><affiliation><nlm:aff id="af1-viruses-11-00031">Key Laboratory of Medical Molecular Virology of MOE/MOH, School of Basic Medical Sciences and Shanghai Public Health Clinical Center, Fudan University, Shanghai 200032, China;<email>16111010068@fudan.edu.cn</email> (C.W.);<email>16211010047@fudan.edu.cn</email> (C.H.);<email>15111010053@fudan.edu.cn</email> (S.X.)</nlm:aff></affiliation></author><author><name sortKey="Jiang, Shibo" sort="Jiang, Shibo" uniqKey="Jiang S" first="Shibo" last="Jiang">Shibo Jiang</name><affiliation><nlm:aff id="af1-viruses-11-00031">Key Laboratory of Medical Molecular Virology of MOE/MOH, School of Basic Medical Sciences and Shanghai Public Health Clinical Center, Fudan University, Shanghai 200032, China;<email>16111010068@fudan.edu.cn</email> (C.W.);<email>16211010047@fudan.edu.cn</email> (C.H.);<email>15111010053@fudan.edu.cn</email> (S.X.)</nlm:aff></affiliation><affiliation><nlm:aff id="af2-viruses-11-00031">NHC Key Laboratory of Reproduction Regulation (Shanghai Institute of Planned Parenthood Research), Fudan University, Shanghai 200032, China;<email>weihua.li@sippr.org.cn</email></nlm:aff></affiliation></author></analytic><series><title level="j">Viruses</title><idno type="eISSN">1999-4915</idno><imprint><date when="2019">2019</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Animals</term><term>Antibodies, Neutralizing (immunology)</term><term>Antibodies, Viral (immunology)</term><term>Drug 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protéines</term><term>Mutation</term><term>Peptides (génétique)</term><term>Peptides (immunologie)</term><term>Pénétration virale</term><term>Souris</term><term>Souris de lignée BALB C</term><term>Synergie des médicaments</term></keywords><keywords scheme="MESH" type="chemical" qualifier="genetics" xml:lang="en"><term>Peptides</term><term>Spike Glycoprotein, Coronavirus</term></keywords><keywords scheme="MESH" type="chemical" qualifier="immunology" xml:lang="en"><term>Antibodies, Neutralizing</term><term>Antibodies, Viral</term><term>Peptides</term><term>Spike Glycoprotein, Coronavirus</term></keywords><keywords scheme="MESH" qualifier="genetics" xml:lang="en"><term>Middle East Respiratory Syndrome Coronavirus</term></keywords><keywords scheme="MESH" qualifier="génétique" xml:lang="fr"><term>Coronavirus du syndrome respiratoire du Moyen-Orient</term><term>Glycoprotéine de spicule des coronavirus</term><term>Peptides</term></keywords><keywords scheme="MESH" qualifier="immunologie" xml:lang="fr"><term>Anticorps antiviraux</term><term>Anticorps neutralisants</term><term>Glycoprotéine de spicule des coronavirus</term><term>Peptides</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Animals</term><term>Drug Synergism</term><term>Female</term><term>HEK293 Cells</term><term>Humans</term><term>Mice</term><term>Mice, Inbred BALB C</term><term>Mutation</term><term>Protein Binding</term><term>Protein Domains</term><term>Virus Internalization</term></keywords><keywords scheme="MESH" xml:lang="fr"><term>Animaux</term><term>Cellules HEK293</term><term>Domaines protéiques</term><term>Femelle</term><term>Humains</term><term>Liaison aux protéines</term><term>Mutation</term><term>Pénétration virale</term><term>Souris</term><term>Souris de lignée BALB C</term><term>Synergie des médicaments</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><p>Middle East respiratory syndrome coronavirus (MERS-CoV) has continuously posed a threat to public health worldwide, yet no therapeutics or vaccines are currently available to prevent or treat MERS-CoV infection. We previously identified a fusion inhibitory peptide (HR2P-M2) targeting the MERS-CoV S2 protein HR1 domain and a highly potent neutralizing monoclonal antibody (m336) specific to the S1 spike protein receptor-binding domain (RBD). However, m336 was found to have reduced efficacy against MERS-CoV strains with mutations in RBD, and HR2P-M2 showed low potency, thus limiting the clinical application of each when administered separately. However, we herein report that the combination of m336 and HR2P-M2 exhibited potent synergism in inhibiting MERS-CoV S protein-mediated cell–cell fusion and infection by MERS-CoV pseudoviruses with or without mutations in the RBD, resulting in the enhancement of antiviral activity in contrast to either one administered alone. Thus, this combinatorial strategy could be used in clinics for the urgent treatment of MERS-CoV-infected patients.</p></div></front><back><div1 type="bibliography"><listBibl><biblStruct><analytic><author><name sortKey="Zaki, A M" uniqKey="Zaki A">A.M. Zaki</name></author><author><name sortKey="Van Boheemen, S" uniqKey="Van Boheemen S">S. van Boheemen</name></author><author><name sortKey="Bestebroer, T M" uniqKey="Bestebroer T">T.M. Bestebroer</name></author><author><name sortKey="Osterhaus, A D" uniqKey="Osterhaus A">A.D. Osterhaus</name></author><author><name sortKey="Fouchier, R A" uniqKey="Fouchier R">R.A. Fouchier</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="De Groot, R J" uniqKey="De Groot R">R.J. de Groot</name></author><author><name sortKey="Baker, S C" uniqKey="Baker S">S.C. Baker</name></author><author><name sortKey="Baric, R S" uniqKey="Baric R">R.S. Baric</name></author><author><name sortKey="Brown, C S" uniqKey="Brown C">C.S. 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Qi</name></author><author><name sortKey="Jiang, S" uniqKey="Jiang S">S. Jiang</name></author></analytic></biblStruct></listBibl></div1></back></TEI><affiliations><list></list><tree><noCountry><name sortKey="Hua, Chen" sort="Hua, Chen" uniqKey="Hua C" first="Chen" last="Hua">Chen Hua</name><name sortKey="Jiang, Shibo" sort="Jiang, Shibo" uniqKey="Jiang S" first="Shibo" last="Jiang">Shibo Jiang</name><name sortKey="Li, Weihua" sort="Li, Weihua" uniqKey="Li W" first="Weihua" last="Li">Weihua Li</name><name sortKey="Lu, Lu" sort="Lu, Lu" uniqKey="Lu L" first="Lu" last="Lu">Lu Lu</name><name sortKey="Wang, Cong" sort="Wang, Cong" uniqKey="Wang C" first="Cong" last="Wang">Cong Wang</name><name sortKey="Xia, Shuai" sort="Xia, Shuai" uniqKey="Xia S" first="Shuai" last="Xia">Shuai Xia</name></noCountry></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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