Anti-hemagglutinin antibody derived lead peptides for inhibitors of influenza virus binding
Antibodies against spike proteins of influenza are used as a tool for characterization of viruses and therapeutic approaches. However, development, production and quality control of antibodies is expensive and time consuming. To circumvent these difficulties, three peptides were derived from complem...
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2016
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| Acceso en línea: | https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_19326203_v11_n7_p_Memczak http://hdl.handle.net/20.500.12110/paper_19326203_v11_n7_p_Memczak |
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paper:paper_19326203_v11_n7_p_Memczak2023-06-08T16:30:36Z Anti-hemagglutinin antibody derived lead peptides for inhibitors of influenza virus binding antivirus agent Influenza virus hemagglutinin antibody derivative peptide PeA peptide PeB peptide PeC unclassified drug virus spike protein epitope Influenza virus hemagglutinin neutralizing antibody virus antibody amino acid substitution animal cell antiviral activity Article binding affinity binding competition circular dichroism complementarity determining region concentration response controlled study drug binding site drug design drug synthesis genetic procedures hemagglutination inhibition test human human cell Influenza A virus Influenza A virus (A/Aichi/2/68(H3N2)) Influenza A virus (A/California/7/2009(H1N1)) Influenza A virus (A/Mute Swan/Rostock/R901/2006(H7N1)) inhibition kinetics microarray analysis molecular dynamics nonhuman protein modification surface plasmon resonance target cell virus cell interaction virus neutralization virus strain animal cell line dog immunology influenza virology virus attachment Animals Antibodies, Neutralizing Antibodies, Viral Cell Line Dogs Epitopes Hemagglutinin Glycoproteins, Influenza Virus Humans Influenza, Human Molecular Dynamics Simulation Virus Attachment Antibodies against spike proteins of influenza are used as a tool for characterization of viruses and therapeutic approaches. However, development, production and quality control of antibodies is expensive and time consuming. To circumvent these difficulties, three peptides were derived from complementarity determining regions of an antibody heavy chain against influenza A spike glycoprotein. Their binding properties were studied experimentally, and by molecular dynamics simulations. Two peptide candidates showed binding to influenza A/Aichi/2/68 H3N2. One of them, termed PeB, with the highest affinity prevented binding to and infection of target cells in the micromolar region without any cytotoxic effect. PeB matches best the conserved receptor binding site of hemagglutinin. PeB bound also to other medical relevant influenza strains, such as human-pathogenic A/California/7/2009 H1N1, and avian-pathogenic A/Mute Swan/Rostock/R901/2006 H7N1. Strategies to improve the affinity and to adapt specificity are discussed and exemplified by a double amino acid substituted peptide, obtained by substitutional analysis. The peptides and their derivatives are of great potential for drug development as well as biosensing. © 2016 Memczak et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. 2016 https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_19326203_v11_n7_p_Memczak http://hdl.handle.net/20.500.12110/paper_19326203_v11_n7_p_Memczak |
| institution |
Universidad de Buenos Aires |
| institution_str |
I-28 |
| repository_str |
R-134 |
| collection |
Biblioteca Digital - Facultad de Ciencias Exactas y Naturales (UBA) |
| topic |
antivirus agent Influenza virus hemagglutinin antibody derivative peptide PeA peptide PeB peptide PeC unclassified drug virus spike protein epitope Influenza virus hemagglutinin neutralizing antibody virus antibody amino acid substitution animal cell antiviral activity Article binding affinity binding competition circular dichroism complementarity determining region concentration response controlled study drug binding site drug design drug synthesis genetic procedures hemagglutination inhibition test human human cell Influenza A virus Influenza A virus (A/Aichi/2/68(H3N2)) Influenza A virus (A/California/7/2009(H1N1)) Influenza A virus (A/Mute Swan/Rostock/R901/2006(H7N1)) inhibition kinetics microarray analysis molecular dynamics nonhuman protein modification surface plasmon resonance target cell virus cell interaction virus neutralization virus strain animal cell line dog immunology influenza virology virus attachment Animals Antibodies, Neutralizing Antibodies, Viral Cell Line Dogs Epitopes Hemagglutinin Glycoproteins, Influenza Virus Humans Influenza, Human Molecular Dynamics Simulation Virus Attachment |
| spellingShingle |
antivirus agent Influenza virus hemagglutinin antibody derivative peptide PeA peptide PeB peptide PeC unclassified drug virus spike protein epitope Influenza virus hemagglutinin neutralizing antibody virus antibody amino acid substitution animal cell antiviral activity Article binding affinity binding competition circular dichroism complementarity determining region concentration response controlled study drug binding site drug design drug synthesis genetic procedures hemagglutination inhibition test human human cell Influenza A virus Influenza A virus (A/Aichi/2/68(H3N2)) Influenza A virus (A/California/7/2009(H1N1)) Influenza A virus (A/Mute Swan/Rostock/R901/2006(H7N1)) inhibition kinetics microarray analysis molecular dynamics nonhuman protein modification surface plasmon resonance target cell virus cell interaction virus neutralization virus strain animal cell line dog immunology influenza virology virus attachment Animals Antibodies, Neutralizing Antibodies, Viral Cell Line Dogs Epitopes Hemagglutinin Glycoproteins, Influenza Virus Humans Influenza, Human Molecular Dynamics Simulation Virus Attachment Anti-hemagglutinin antibody derived lead peptides for inhibitors of influenza virus binding |
| topic_facet |
antivirus agent Influenza virus hemagglutinin antibody derivative peptide PeA peptide PeB peptide PeC unclassified drug virus spike protein epitope Influenza virus hemagglutinin neutralizing antibody virus antibody amino acid substitution animal cell antiviral activity Article binding affinity binding competition circular dichroism complementarity determining region concentration response controlled study drug binding site drug design drug synthesis genetic procedures hemagglutination inhibition test human human cell Influenza A virus Influenza A virus (A/Aichi/2/68(H3N2)) Influenza A virus (A/California/7/2009(H1N1)) Influenza A virus (A/Mute Swan/Rostock/R901/2006(H7N1)) inhibition kinetics microarray analysis molecular dynamics nonhuman protein modification surface plasmon resonance target cell virus cell interaction virus neutralization virus strain animal cell line dog immunology influenza virology virus attachment Animals Antibodies, Neutralizing Antibodies, Viral Cell Line Dogs Epitopes Hemagglutinin Glycoproteins, Influenza Virus Humans Influenza, Human Molecular Dynamics Simulation Virus Attachment |
| description |
Antibodies against spike proteins of influenza are used as a tool for characterization of viruses and therapeutic approaches. However, development, production and quality control of antibodies is expensive and time consuming. To circumvent these difficulties, three peptides were derived from complementarity determining regions of an antibody heavy chain against influenza A spike glycoprotein. Their binding properties were studied experimentally, and by molecular dynamics simulations. Two peptide candidates showed binding to influenza A/Aichi/2/68 H3N2. One of them, termed PeB, with the highest affinity prevented binding to and infection of target cells in the micromolar region without any cytotoxic effect. PeB matches best the conserved receptor binding site of hemagglutinin. PeB bound also to other medical relevant influenza strains, such as human-pathogenic A/California/7/2009 H1N1, and avian-pathogenic A/Mute Swan/Rostock/R901/2006 H7N1. Strategies to improve the affinity and to adapt specificity are discussed and exemplified by a double amino acid substituted peptide, obtained by substitutional analysis. The peptides and their derivatives are of great potential for drug development as well as biosensing. © 2016 Memczak et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. |
| title |
Anti-hemagglutinin antibody derived lead peptides for inhibitors of influenza virus binding |
| title_short |
Anti-hemagglutinin antibody derived lead peptides for inhibitors of influenza virus binding |
| title_full |
Anti-hemagglutinin antibody derived lead peptides for inhibitors of influenza virus binding |
| title_fullStr |
Anti-hemagglutinin antibody derived lead peptides for inhibitors of influenza virus binding |
| title_full_unstemmed |
Anti-hemagglutinin antibody derived lead peptides for inhibitors of influenza virus binding |
| title_sort |
anti-hemagglutinin antibody derived lead peptides for inhibitors of influenza virus binding |
| publishDate |
2016 |
| url |
https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_19326203_v11_n7_p_Memczak http://hdl.handle.net/20.500.12110/paper_19326203_v11_n7_p_Memczak |
| _version_ |
1768541818911195136 |