Dual-Action Heteromultivalent Glycopolymers Stringently Block and Arrest Influenza A Virus Infection In Vitro and Ex Vivo .

Autor:	Parshad B; Institut für Chemie und Biochemie Organische Chemie, Freie Universität Berlin, Takustr. 3, 14195 Berlin, Germany.; Wellman Center for Photomedicine, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts 02129, United States., Schlecht MN; Unit 17, Influenza and Other Respiratory Viruses, Robert Koch-Institut, Seestraße 10, 13353 Berlin, Germany.; Medical Clinic III, Division of Nephrology, Medizinische Fakultät Carl Gustav Carus an der TU Dresden, Fiedlerstr. 40, 01307 Dresden, Germany., Baumgardt M; Department of Infectious Diseases, Respiratory Medicine and Critical Care, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, 10117 Berlin, Germany., Ludwig K; Forschungszentrum für Elektronenmikroskopie and Core Facility BioSupraMol, Institut für Chemie und Biochemie, Freie Universität Berlin, Fabeckstr. 36a, 14195 Berlin, Germany., Nie C; Institut für Chemie und Biochemie Organische Chemie, Freie Universität Berlin, Takustr. 3, 14195 Berlin, Germany., Rimondi A; Unit 17, Influenza and Other Respiratory Viruses, Robert Koch-Institut, Seestraße 10, 13353 Berlin, Germany., Hönzke K; Department of Infectious Diseases, Respiratory Medicine and Critical Care, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, 10117 Berlin, Germany., Angioletti-Uberti S; Department of Materials, Imperial College London, London SW7 2AZ, U.K., Khatri V; Institut für Chemie und Biochemie Organische Chemie, Freie Universität Berlin, Takustr. 3, 14195 Berlin, Germany., Schneider P; Department for Thoracic Surgery, DRK Clinics, 13359 Berlin, Germany., Herrmann A; Institut für Chemie und Biochemie Organische Chemie, Freie Universität Berlin, Takustr. 3, 14195 Berlin, Germany., Haag R; Institut für Chemie und Biochemie Organische Chemie, Freie Universität Berlin, Takustr. 3, 14195 Berlin, Germany., Hocke AC; Department of Infectious Diseases, Respiratory Medicine and Critical Care, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, 10117 Berlin, Germany., Wolff T; Unit 17, Influenza and Other Respiratory Viruses, Robert Koch-Institut, Seestraße 10, 13353 Berlin, Germany., Bhatia S; Institut für Chemie und Biochemie Organische Chemie, Freie Universität Berlin, Takustr. 3, 14195 Berlin, Germany.
Jazyk:	angličtina
Zdroj:	Nano letters [Nano Lett] 2023 Jun 14; Vol. 23 (11), pp. 4844-4853. Date of Electronic Publication: 2023 May 23.
DOI:	10.1021/acs.nanolett.3c00408
Abstrakt:	Here, we demonstrate the concerted inhibition of different influenza A virus (IAV) strains using a low-molecular-weight dual-action linear polymer. The 6'-sialyllactose and zanamivir conjugates of linear polyglycerol are optimized for simultaneous targeting of hemagglutinin and neuraminidase on the IAV surface. Independent of IAV subtypes, hemagglutination inhibition data suggest better adsorption of the heteromultivalent polymer than homomultivalent analogs onto the virus surface. Cryo-TEM images imply heteromultivalent compound-mediated virus aggregation. The optimized polymeric nanomaterial inhibits >99.9% propagation of various IAV strains 24 h postinfection in vitro at low nM concentrations and is up to 10000× more effective than the commercial zanamivir drug. In a human lung ex vivo multicyclic infection setup, the heteromultivalent polymer outperforms the commercial drug zanamivir and homomultivalent analogs or their physical mixtures. This study authenticates the translational potential of the dual-action targeting approach using small polymers for broad and high antiviral efficacy.
Databáze:	MEDLINE
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