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Antiviral potential of 3′-sialyllactose- and 6′-sialyllactose-conjugated dendritic polymers against human and avian influenza viruses

Current treatment options for influenza virus infections in humans are limited and therefore the development of novel antivirals is of high priority. Inhibiting influenza virus attachment to host cells would provide an early and efficient block of the infection and thus, receptor analogs have been c...

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Autores principales: Günther, Sira Carolin, Maier, Julian David, Vetter, Janine, Podvalnyy, Nikita, Khanzhin, Nikolay, Hennet, Thierry, Stertz, Silke
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6972948/
https://www.ncbi.nlm.nih.gov/pubmed/31964943
http://dx.doi.org/10.1038/s41598-020-57608-4
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author Günther, Sira Carolin
Maier, Julian David
Vetter, Janine
Podvalnyy, Nikita
Khanzhin, Nikolay
Hennet, Thierry
Stertz, Silke
author_facet Günther, Sira Carolin
Maier, Julian David
Vetter, Janine
Podvalnyy, Nikita
Khanzhin, Nikolay
Hennet, Thierry
Stertz, Silke
author_sort Günther, Sira Carolin
collection PubMed
description Current treatment options for influenza virus infections in humans are limited and therefore the development of novel antivirals is of high priority. Inhibiting influenza virus attachment to host cells would provide an early and efficient block of the infection and thus, receptor analogs have been considered as options for antiviral treatment. Here, we describe the rapid and efficient synthesis of PAMAM dendrimers conjugated with either 3′-sialyllactose (3SL) or 6′-sialyllactose (6SL) and their potential to inhibit a diverse range of human and avian influenza virus strains. We show in a hemagglutination inhibition (HAI) assay that human IAV strains can be inhibited by (6SL)- and to a lesser extent also by (3SL)-conjugated PAMAM dendrimers. In contrast, avian strains could only be inhibited by (3SL)-conjugated dendrimers. Importantly, the differential sensitivities of human and avian IAV to the two types of sialyllactose-conjugated dendrimers could be confirmed in cell-based neutralization assays. Based on our findings, we suggest to further develop both, (3SL)- and (6SL)-conjugated PAMAM dendrimers, as influenza virus inhibitors.
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spelling pubmed-69729482020-01-27 Antiviral potential of 3′-sialyllactose- and 6′-sialyllactose-conjugated dendritic polymers against human and avian influenza viruses Günther, Sira Carolin Maier, Julian David Vetter, Janine Podvalnyy, Nikita Khanzhin, Nikolay Hennet, Thierry Stertz, Silke Sci Rep Article Current treatment options for influenza virus infections in humans are limited and therefore the development of novel antivirals is of high priority. Inhibiting influenza virus attachment to host cells would provide an early and efficient block of the infection and thus, receptor analogs have been considered as options for antiviral treatment. Here, we describe the rapid and efficient synthesis of PAMAM dendrimers conjugated with either 3′-sialyllactose (3SL) or 6′-sialyllactose (6SL) and their potential to inhibit a diverse range of human and avian influenza virus strains. We show in a hemagglutination inhibition (HAI) assay that human IAV strains can be inhibited by (6SL)- and to a lesser extent also by (3SL)-conjugated PAMAM dendrimers. In contrast, avian strains could only be inhibited by (3SL)-conjugated dendrimers. Importantly, the differential sensitivities of human and avian IAV to the two types of sialyllactose-conjugated dendrimers could be confirmed in cell-based neutralization assays. Based on our findings, we suggest to further develop both, (3SL)- and (6SL)-conjugated PAMAM dendrimers, as influenza virus inhibitors. Nature Publishing Group UK 2020-01-21 /pmc/articles/PMC6972948/ /pubmed/31964943 http://dx.doi.org/10.1038/s41598-020-57608-4 Text en © The Author(s) 2020 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
Günther, Sira Carolin
Maier, Julian David
Vetter, Janine
Podvalnyy, Nikita
Khanzhin, Nikolay
Hennet, Thierry
Stertz, Silke
Antiviral potential of 3′-sialyllactose- and 6′-sialyllactose-conjugated dendritic polymers against human and avian influenza viruses
title Antiviral potential of 3′-sialyllactose- and 6′-sialyllactose-conjugated dendritic polymers against human and avian influenza viruses
title_full Antiviral potential of 3′-sialyllactose- and 6′-sialyllactose-conjugated dendritic polymers against human and avian influenza viruses
title_fullStr Antiviral potential of 3′-sialyllactose- and 6′-sialyllactose-conjugated dendritic polymers against human and avian influenza viruses
title_full_unstemmed Antiviral potential of 3′-sialyllactose- and 6′-sialyllactose-conjugated dendritic polymers against human and avian influenza viruses
title_short Antiviral potential of 3′-sialyllactose- and 6′-sialyllactose-conjugated dendritic polymers against human and avian influenza viruses
title_sort antiviral potential of 3′-sialyllactose- and 6′-sialyllactose-conjugated dendritic polymers against human and avian influenza viruses
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6972948/
https://www.ncbi.nlm.nih.gov/pubmed/31964943
http://dx.doi.org/10.1038/s41598-020-57608-4
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