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Topology‐Matching Design of an Influenza‐Neutralizing Spiky Nanoparticle‐Based Inhibitor with a Dual Mode of Action

Chuanxiong Nie, Badri Parshad, Sumati Bhatia Orcid Logo, Chong Cheng, Marlena Stadtmüller, Alexander Oehrl, Yannic Kerkhoff, Thorsten Wolff, Rainer Haag Orcid Logo

Angewandte Chemie International Edition, Volume: 59, Issue: 36, Pages: 15532 - 15536

Swansea University Author: Sumati Bhatia Orcid Logo

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DOI (Published version): 10.1002/anie.202004832

Abstract

In this study, we demonstrate the concept of “topology-matching design” for virus inhibitors. With the current knowledge of influenza A virus (IAV), we designed a nanoparticle-based inhibitor (nano-inhibitor) that has a matched nanotopology to IAV virions and shows heteromultivalent inhibitory effec...

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Published in: Angewandte Chemie International Edition
ISSN: 1433-7851 1521-3773
Published: Wiley 2020
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URI: https://cronfa.swan.ac.uk/Record/cronfa64863
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spelling v2 64863 2023-11-01 Topology‐Matching Design of an Influenza‐Neutralizing Spiky Nanoparticle‐Based Inhibitor with a Dual Mode of Action a6b1181ebdbe42bd03b24cbdb559d082 0000-0002-5123-4937 Sumati Bhatia Sumati Bhatia true false 2023-11-01 CHEM In this study, we demonstrate the concept of “topology-matching design” for virus inhibitors. With the current knowledge of influenza A virus (IAV), we designed a nanoparticle-based inhibitor (nano-inhibitor) that has a matched nanotopology to IAV virions and shows heteromultivalent inhibitory effects on hemagglutinin and neuraminidase. The synthesized nano-inhibitor can neutralize the viral particle extracellularly and block its attachment and entry to the host cells. The virus replication was significantly reduced by 6 orders of magnitude in the presence of the reverse designed nano-inhibitors. Even when used 24 hours after the infection, more than 99.999 % inhibition is still achieved, which indicates such a nano-inhibitor might be a potent antiviral for the treatment of influenza infection. Journal Article Angewandte Chemie International Edition 59 36 15532 15536 Wiley 1433-7851 1521-3773 Antiviral agents, inhibitors, influenza, nanoparticles, topology matching 25 8 2020 2020-08-25 10.1002/anie.202004832 http://dx.doi.org/10.1002/anie.202004832 COLLEGE NANME Chemistry COLLEGE CODE CHEM Swansea University The authors gratefully acknowledge financial support from Deutsche Forschungsgemeinschaft (DFG) through grants within the Collaborative Research Center (SFB) 765. C.N. acknowledges the support from China Scholarship Council (CSC). We would like to acknowledge the assistance of the Core Facility BioSupraMol supported by the DFG. Open access funding enabled and organized by Projekt DEAL. 2024-01-02T13:17:12.2756299 2023-11-01T10:38:37.4410010 Faculty of Science and Engineering School of Engineering and Applied Sciences - Chemistry Chuanxiong Nie 1 Badri Parshad 2 Sumati Bhatia 0000-0002-5123-4937 3 Chong Cheng 4 Marlena Stadtmüller 5 Alexander Oehrl 6 Yannic Kerkhoff 7 Thorsten Wolff 8 Rainer Haag 0000-0003-3840-162x 9 64863__29333__7862d30a2fc9424ea7609b88d3cef012.pdf 64863.VOR.pdf 2024-01-02T10:48:46.9438694 Output 2491216 application/pdf Version of Record true © 2020 The Authors. Published by Wiley-VCH Verlag GmbH & Co. KGaA. Distributed under the terms of a Creative Commons Attribution 4.0 International License (CC BY 4.0). true eng https://creativecommons.org/licenses/by/4.0/
title Topology‐Matching Design of an Influenza‐Neutralizing Spiky Nanoparticle‐Based Inhibitor with a Dual Mode of Action
spellingShingle Topology‐Matching Design of an Influenza‐Neutralizing Spiky Nanoparticle‐Based Inhibitor with a Dual Mode of Action
Sumati Bhatia
title_short Topology‐Matching Design of an Influenza‐Neutralizing Spiky Nanoparticle‐Based Inhibitor with a Dual Mode of Action
title_full Topology‐Matching Design of an Influenza‐Neutralizing Spiky Nanoparticle‐Based Inhibitor with a Dual Mode of Action
title_fullStr Topology‐Matching Design of an Influenza‐Neutralizing Spiky Nanoparticle‐Based Inhibitor with a Dual Mode of Action
title_full_unstemmed Topology‐Matching Design of an Influenza‐Neutralizing Spiky Nanoparticle‐Based Inhibitor with a Dual Mode of Action
title_sort Topology‐Matching Design of an Influenza‐Neutralizing Spiky Nanoparticle‐Based Inhibitor with a Dual Mode of Action
author_id_str_mv a6b1181ebdbe42bd03b24cbdb559d082
author_id_fullname_str_mv a6b1181ebdbe42bd03b24cbdb559d082_***_Sumati Bhatia
author Sumati Bhatia
author2 Chuanxiong Nie
Badri Parshad
Sumati Bhatia
Chong Cheng
Marlena Stadtmüller
Alexander Oehrl
Yannic Kerkhoff
Thorsten Wolff
Rainer Haag
format Journal article
container_title Angewandte Chemie International Edition
container_volume 59
container_issue 36
container_start_page 15532
publishDate 2020
institution Swansea University
issn 1433-7851
1521-3773
doi_str_mv 10.1002/anie.202004832
publisher Wiley
college_str Faculty of Science and Engineering
hierarchytype
hierarchy_top_id facultyofscienceandengineering
hierarchy_top_title Faculty of Science and Engineering
hierarchy_parent_id facultyofscienceandengineering
hierarchy_parent_title Faculty of Science and Engineering
department_str School of Engineering and Applied Sciences - Chemistry{{{_:::_}}}Faculty of Science and Engineering{{{_:::_}}}School of Engineering and Applied Sciences - Chemistry
url http://dx.doi.org/10.1002/anie.202004832
document_store_str 1
active_str 0
description In this study, we demonstrate the concept of “topology-matching design” for virus inhibitors. With the current knowledge of influenza A virus (IAV), we designed a nanoparticle-based inhibitor (nano-inhibitor) that has a matched nanotopology to IAV virions and shows heteromultivalent inhibitory effects on hemagglutinin and neuraminidase. The synthesized nano-inhibitor can neutralize the viral particle extracellularly and block its attachment and entry to the host cells. The virus replication was significantly reduced by 6 orders of magnitude in the presence of the reverse designed nano-inhibitors. Even when used 24 hours after the infection, more than 99.999 % inhibition is still achieved, which indicates such a nano-inhibitor might be a potent antiviral for the treatment of influenza infection.
published_date 2020-08-25T13:17:14Z
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score 11.013731

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