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Heteromultivalent topology-matched nanostructures as potent and broad-spectrum influenza A virus inhibitors

Chuanxiong Nie Orcid Logo, Marlena Stadtmüller Orcid Logo, Badri Parshad Orcid Logo, Matthias Wallert, Vahid Ahmadi Orcid Logo, Yannic Kerkhoff Orcid Logo, Sumati Bhatia Orcid Logo, Stephan Block Orcid Logo, Chong Cheng Orcid Logo, Thorsten Wolff Orcid Logo, Rainer Haag Orcid Logo

Science Advances, Volume: 7, Issue: 1

Swansea University Author: Sumati Bhatia Orcid Logo

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DOI (Published version): 10.1126/sciadv.abd3803

Abstract

Here, we report the topology-matched design of heteromultivalent nanostructures as potent and broad-spectrum virus entry inhibitors based on the host cell membrane. Initially, we investigate the virus binding dynamics to validate the better binding performance of the heteromultivalent moieties as co...

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Published in: Science Advances
ISSN: 2375-2548
Published: American Association for the Advancement of Science (AAAS) 2021
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spelling v2 64862 2023-11-01 Heteromultivalent topology-matched nanostructures as potent and broad-spectrum influenza A virus inhibitors a6b1181ebdbe42bd03b24cbdb559d082 0000-0002-5123-4937 Sumati Bhatia Sumati Bhatia true false 2023-11-01 CHEM Here, we report the topology-matched design of heteromultivalent nanostructures as potent and broad-spectrum virus entry inhibitors based on the host cell membrane. Initially, we investigate the virus binding dynamics to validate the better binding performance of the heteromultivalent moieties as compared to homomultivalent ones. The heteromultivalent binding moieties are transferred to nanostructures with a bowl-like shape matching the viral spherical surface. Unlike the conventional homomultivalent inhibitors, the heteromultivalent ones exhibit a half maximal inhibitory concentration of 32.4 ± 13.7 μg/ml due to the synergistic multivalent effects and the topology-matched shape. At a dose without causing cellular toxicity, >99.99% reduction of virus propagation has been achieved. Since multiple binding sites have also been identified on the S protein of SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2), we envision that the use of heteromultivalent nanostructures may also be applied to develop a potent inhibitor to prevent coronavirus infection. Journal Article Science Advances 7 1 American Association for the Advancement of Science (AAAS) 2375-2548 1 1 2021 2021-01-01 10.1126/sciadv.abd3803 http://dx.doi.org/10.1126/sciadv.abd3803 COLLEGE NANME Chemistry COLLEGE CODE CHEM Swansea University The authors gratefully acknowledge financial support from DFG through grants from the Collaborative Research Center (SFB) 765. S. Bl. acknowledges the support of DFG through grant BL1514/1. C.N. acknowledges the support from the China Scholarship Council (CSC). C.C. acknowledges the support of the National Key R&D Program of China (2019YFA0110600 and 2019YFA0110601), the Science and Technology Project of Sichuan Province (2020YFH0087 and 2020YJ0055), Special Funds for Prevention and Control of COVID-19 of Sichuan University (2020scunCoV-YJ-20005), and SKLFPM, Donghua University (YJ202005), State Key Laboratory of Polymer Materials Engineering (grant no. sklpme2019-2-03), Fundamental Research Funds for the Central Universities, Ten Thousand Youth Talents Plan, and Alexander von Humboldt Fellowship. 2024-01-02T11:23:46.9267600 2023-11-01T10:38:17.7215116 Faculty of Science and Engineering School of Engineering and Applied Sciences - Chemistry Chuanxiong Nie 0000-0001-7963-1187 1 Marlena Stadtmüller 0000-0001-8893-5326 2 Badri Parshad 0000-0001-6496-8844 3 Matthias Wallert 4 Vahid Ahmadi 0000-0002-2627-2368 5 Yannic Kerkhoff 0000-0002-8126-2082 6 Sumati Bhatia 0000-0002-5123-4937 7 Stephan Block 0000-0002-2947-0837 8 Chong Cheng 0000-0002-6872-2240 9 Thorsten Wolff 0000-0001-7688-236x 10 Rainer Haag 0000-0003-3840-162x 11 64862__29335__80a192327b174c06a5594474539e425b.pdf 64862.VOR.pdf 2024-01-02T11:01:36.0730245 Output 2925691 application/pdf Version of Record true Copyright © 2021 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. Distributed under the terms of a Creative Commons Attribution Non Commercial 4.0 License (CC BY-NC 4.0). true eng https://creativecommons.org/licenses/by-nc/4.0/
title Heteromultivalent topology-matched nanostructures as potent and broad-spectrum influenza A virus inhibitors
spellingShingle Heteromultivalent topology-matched nanostructures as potent and broad-spectrum influenza A virus inhibitors
Sumati Bhatia
title_short Heteromultivalent topology-matched nanostructures as potent and broad-spectrum influenza A virus inhibitors
title_full Heteromultivalent topology-matched nanostructures as potent and broad-spectrum influenza A virus inhibitors
title_fullStr Heteromultivalent topology-matched nanostructures as potent and broad-spectrum influenza A virus inhibitors
title_full_unstemmed Heteromultivalent topology-matched nanostructures as potent and broad-spectrum influenza A virus inhibitors
title_sort Heteromultivalent topology-matched nanostructures as potent and broad-spectrum influenza A virus inhibitors
author_id_str_mv a6b1181ebdbe42bd03b24cbdb559d082
author_id_fullname_str_mv a6b1181ebdbe42bd03b24cbdb559d082_***_Sumati Bhatia
author Sumati Bhatia
author2 Chuanxiong Nie
Marlena Stadtmüller
Badri Parshad
Matthias Wallert
Vahid Ahmadi
Yannic Kerkhoff
Sumati Bhatia
Stephan Block
Chong Cheng
Thorsten Wolff
Rainer Haag
format Journal article
container_title Science Advances
container_volume 7
container_issue 1
publishDate 2021
institution Swansea University
issn 2375-2548
doi_str_mv 10.1126/sciadv.abd3803
publisher American Association for the Advancement of Science (AAAS)
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/10.1126/sciadv.abd3803
document_store_str 1
active_str 0
description Here, we report the topology-matched design of heteromultivalent nanostructures as potent and broad-spectrum virus entry inhibitors based on the host cell membrane. Initially, we investigate the virus binding dynamics to validate the better binding performance of the heteromultivalent moieties as compared to homomultivalent ones. The heteromultivalent binding moieties are transferred to nanostructures with a bowl-like shape matching the viral spherical surface. Unlike the conventional homomultivalent inhibitors, the heteromultivalent ones exhibit a half maximal inhibitory concentration of 32.4 ± 13.7 μg/ml due to the synergistic multivalent effects and the topology-matched shape. At a dose without causing cellular toxicity, >99.99% reduction of virus propagation has been achieved. Since multiple binding sites have also been identified on the S protein of SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2), we envision that the use of heteromultivalent nanostructures may also be applied to develop a potent inhibitor to prevent coronavirus infection.
published_date 2021-01-01T11:23:48Z
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score 11.037056

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