Nanoengineered Red Blood Cells Loaded with TMPRSS2 and Cathepsin L Inhibitors Block SARS-CoV-2 Pseudovirus Entry into Lung ACE2 + Cells.

Autor: Yang H; Stem Cell and Regenerative Medicine Lab, Beijing Institute of Radiation Medicine, Beijing, 100850, China., Zhou JN; Stem Cell and Regenerative Medicine Lab, Beijing Institute of Radiation Medicine, Beijing, 100850, China., Zhang XM; Stem Cell and Regenerative Medicine Lab, Beijing Institute of Radiation Medicine, Beijing, 100850, China., Ling DD; Department of Pharmaceutical Sciences, Beijing Institute of Radiation Medicine, Beijing, 100850, China., Sun YB; Department of Pharmaceutical Sciences, Beijing Institute of Radiation Medicine, Beijing, 100850, China., Li CY; Institute of Health Service and Transfusion Medicine, Beijing, 100850, China., Zhou QQ; Institute of Health Service and Transfusion Medicine, Beijing, 100850, China., Shi GN; State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, 100050, China., Wang SH; Stem Cell and Regenerative Medicine Lab, Beijing Institute of Radiation Medicine, Beijing, 100850, China., Lin XS; Stem Cell and Regenerative Medicine Lab, Beijing Institute of Radiation Medicine, Beijing, 100850, China., Fan T; Stem Cell and Regenerative Medicine Lab, Beijing Institute of Radiation Medicine, Beijing, 100850, China., Wang HY; Stem Cell and Regenerative Medicine Lab, Beijing Institute of Radiation Medicine, Beijing, 100850, China., Zeng Q; Stem Cell and Regenerative Medicine Lab, Beijing Institute of Radiation Medicine, Beijing, 100850, China., Jia YL; Stem Cell and Regenerative Medicine Lab, Beijing Institute of Radiation Medicine, Beijing, 100850, China., Xi JF; Stem Cell and Regenerative Medicine Lab, Beijing Institute of Radiation Medicine, Beijing, 100850, China., Jin YG; Department of Pharmaceutical Sciences, Beijing Institute of Radiation Medicine, Beijing, 100850, China., Pei XT; Stem Cell and Regenerative Medicine Lab, Beijing Institute of Radiation Medicine, Beijing, 100850, China., Yue W; Stem Cell and Regenerative Medicine Lab, Beijing Institute of Radiation Medicine, Beijing, 100850, China.
Jazyk: angličtina
Zdroj: Advanced materials (Deerfield Beach, Fla.) [Adv Mater] 2024 Apr; Vol. 36 (15), pp. e2310306. Date of Electronic Publication: 2024 Jan 17.
DOI: 10.1002/adma.202310306
Abstrakt: 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.
(© 2024 The Authors. Advanced Materials published by Wiley‐VCH GmbH.)
Databáze: MEDLINE
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