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Topology‐Matching Design of an Influenza‐Neutralizing Spiky Nanoparticle‐Based Inhibitor with a Dual Mode of Action
Angewandte Chemie International Edition, Volume: 59, Issue: 36, Pages: 15532 - 15536
Swansea University Author: Sumati Bhatia
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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...
Published in: | Angewandte Chemie International Edition |
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ISSN: | 1433-7851 1521-3773 |
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Wiley
2020
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URI: | https://cronfa.swan.ac.uk/Record/cronfa64863 |
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2024-01-02T13:17:12.2756299 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 EAAS 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 Engineering and Applied Sciences School COLLEGE CODE EAAS 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 |
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a6b1181ebdbe42bd03b24cbdb559d082 |
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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 |
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Angewandte Chemie International Edition |
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15532 |
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1433-7851 1521-3773 |
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10.1002/anie.202004832 |
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Wiley |
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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 |
2020-08-25T20:26:10Z |
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