Nanoengineered Red Blood Cells Loaded with TMPRSS2 and Cathepsin L Inhibitors Block SARS-CoV-2 Pseudovirus Entry into Lung ACE2+ Cells
© 2024 The Authors. Advanced Materials published by Wiley‐VCH GmbH..
The enzymatic activities of Furin, Transmembrane serine proteinase 2 (TMPRSS2), Cathepsin L (CTSL), and Angiotensin-converting enzyme 2 (ACE2) receptor binding are necessary for the entry of coronaviruses into host cells. Precise inhibition of these key proteases in ACE2+ lung cells during a viral infection cycle shall prevent viral Spike (S) protein activation and its fusion with a host cell membrane, consequently averting virus entry to the cells. In this study, dual-drug-combined (TMPRSS2 inhibitor Camostat and CTSL inhibitor E-64d) nanocarriers (NCs) are constructed conjugated with an anti-human ACE2 (hACE2) antibody and employ Red Blood Cell (RBC)-hitchhiking, termed "Nanoengineered RBCs," for targeting lung cells. The significant therapeutic efficacy of the dual-drug-loaded nanoengineered RBCs in pseudovirus-infected K18-hACE2 transgenic mice is reported. Notably, the modular nanoengineered RBCs (anti-receptor antibody+NCs+RBCs) precisely target key proteases of host cells in the lungs to block the entry of Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), regardless of virus variations. These findings are anticipated to benefit the development of a series of novel and safe host-cell-protecting antiviral therapies.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2024 |
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| Erschienen: |
2024 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:36 |
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| Enthalten in: |
Advanced materials (Deerfield Beach, Fla.) - 36(2024), 15 vom: 01. Apr., Seite e2310306 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Yang, Hui [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 15.04.2024 Date Revised 23.04.2024 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1002/adma.202310306 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| 245 | 1 | 0 | |a Nanoengineered Red Blood Cells Loaded with TMPRSS2 and Cathepsin L Inhibitors Block SARS-CoV-2 Pseudovirus Entry into Lung ACE2+ Cells |
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| 520 | |a © 2024 The Authors. Advanced Materials published by Wiley‐VCH GmbH. | ||
| 520 | |a The enzymatic activities of Furin, Transmembrane serine proteinase 2 (TMPRSS2), Cathepsin L (CTSL), and Angiotensin-converting enzyme 2 (ACE2) receptor binding are necessary for the entry of coronaviruses into host cells. Precise inhibition of these key proteases in ACE2+ lung cells during a viral infection cycle shall prevent viral Spike (S) protein activation and its fusion with a host cell membrane, consequently averting virus entry to the cells. In this study, dual-drug-combined (TMPRSS2 inhibitor Camostat and CTSL inhibitor E-64d) nanocarriers (NCs) are constructed conjugated with an anti-human ACE2 (hACE2) antibody and employ Red Blood Cell (RBC)-hitchhiking, termed "Nanoengineered RBCs," for targeting lung cells. The significant therapeutic efficacy of the dual-drug-loaded nanoengineered RBCs in pseudovirus-infected K18-hACE2 transgenic mice is reported. Notably, the modular nanoengineered RBCs (anti-receptor antibody+NCs+RBCs) precisely target key proteases of host cells in the lungs to block the entry of Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), regardless of virus variations. These findings are anticipated to benefit the development of a series of novel and safe host-cell-protecting antiviral therapies | ||
| 650 | 4 | |a Journal Article | |
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| 650 | 4 | |a Cathepsin L | |
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| 700 | 1 | |a Zhou, Jun-Nian |e verfasserin |4 aut | |
| 700 | 1 | |a Zhang, Xue-Mei |e verfasserin |4 aut | |
| 700 | 1 | |a Ling, Dan-Dan |e verfasserin |4 aut | |
| 700 | 1 | |a Sun, Ying-Bao |e verfasserin |4 aut | |
| 700 | 1 | |a Li, Chen-Yan |e verfasserin |4 aut | |
| 700 | 1 | |a Zhou, Qian-Qian |e verfasserin |4 aut | |
| 700 | 1 | |a Shi, Gao-Na |e verfasserin |4 aut | |
| 700 | 1 | |a Wang, Si-Han |e verfasserin |4 aut | |
| 700 | 1 | |a Lin, Xiao-Song |e verfasserin |4 aut | |
| 700 | 1 | |a Fan, Tao |e verfasserin |4 aut | |
| 700 | 1 | |a Wang, Hai-Yang |e verfasserin |4 aut | |
| 700 | 1 | |a Zeng, Quan |e verfasserin |4 aut | |
| 700 | 1 | |a Jia, Ya-Li |e verfasserin |4 aut | |
| 700 | 1 | |a Xi, Jia-Fei |e verfasserin |4 aut | |
| 700 | 1 | |a Jin, Yi-Guang |e verfasserin |4 aut | |
| 700 | 1 | |a Pei, Xue-Tao |e verfasserin |4 aut | |
| 700 | 1 | |a Yue, Wen |e verfasserin |4 aut | |
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