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Heteromultivalent topology-matched nanostructures as potent and broad-spectrum influenza A virus inhibitors
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Marlena Stadtmüller ,
Badri Parshad ,
Matthias Wallert,
Vahid Ahmadi ,
Yannic Kerkhoff ,
Sumati Bhatia ,
Stephan Block ,
Chong Cheng ,
Thorsten Wolff ,
Rainer Haag
Science Advances, Volume: 7, Issue: 1
Swansea University Author:
Sumati Bhatia
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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).
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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...
| Published in: | Science Advances |
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| ISSN: | 2375-2548 |
| Published: |
American Association for the Advancement of Science (AAAS)
2021
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| Online Access: |
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| URI: | https://cronfa.swan.ac.uk/Record/cronfa64862 |
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| 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 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. |
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| College: |
Faculty of Science and Engineering |
| Funders: |
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. |
| Issue: |
1 |