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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 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/MuteSwan/Rostock/R901/2006 H7N1. Strategies to improve the affinity and to adapt specificity are discussed and exemplified by aAntibodies 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/MuteSwan/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.show moreshow less

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Metadaten
Author:Henry MemczakGND, Daniel Lauster, Parimal KarORCiD, Santiago Di Lella, Rudolf Volkmer, Volker Knecht, Andreas Herrmann, Eva Ehrentreich-Förster, Frank Fabian BierORCiDGND, Walter F. M. Stöcklein
URN:urn:nbn:de:kobv:517-opus4-410872
DOI:https://doi.org/10.25932/publishup-41087
ISSN:1866-8372
Parent Title (English):Postprints der Universität Potsdam : Mathematisch-Naturwissenschaftliche Reihe
Series (Serial Number):Postprints der Universität Potsdam : Mathematisch-Naturwissenschaftliche Reihe (536)
Document Type:Postprint
Language:English
Date of first Publication:2019/01/18
Year of Completion:2016
Publishing Institution:Universität Potsdam
Release Date:2019/01/18
Tag:A viruses; avian influenza; entry; identification; invection; neuraminidase; neutralizing antibody; origin; receptor-binding; sites
Issue:536
Pagenumber:24
Source:PLOS ONE 11 (2016) 7, Art. e0159074 DOI 10.1371/journal.pone.0159074
Organizational units:Mathematisch-Naturwissenschaftliche Fakultät
Dewey Decimal Classification:5 Naturwissenschaften und Mathematik / 50 Naturwissenschaften / 500 Naturwissenschaften und Mathematik
6 Technik, Medizin, angewandte Wissenschaften / 61 Medizin und Gesundheit / 610 Medizin und Gesundheit
Peer Review:Referiert
Publication Way:Open Access
Grantor:Public Library of Science (PLOS)
Licence (German):License LogoCreative Commons - Namensnennung, 4.0 International