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Inhalable nanocatchers for SARS-CoV-2 inhibition.
Proc Natl Acad Sci U S A. 2021 07 20; 118(29)PN

Abstract

The global coronavirus disease 2019 (COVID-19) pandemic, caused by severe acute respiratory syndrome (SARS)-like coronavirus (SARS-CoV-2), presents an urgent health crisis. More recently, an increasing number of mutated strains of SARS-CoV-2 have been identified globally. Such mutations, especially those on the spike glycoprotein to render its higher binding affinity to human angiotensin-converting enzyme II (hACE2) receptors, not only resulted in higher transmission of SARS-CoV-2 but also raised serious concerns regarding the efficacies of vaccines against mutated viruses. Since ACE2 is the virus-binding protein on human cells regardless of viral mutations, we design hACE2-containing nanocatchers (NCs) as the competitor with host cells for virus binding to protect cells from SARS-CoV-2 infection. The hACE2-containing NCs, derived from the cellular membrane of genetically engineered cells stably expressing hACE2, exhibited excellent neutralization ability against pseudoviruses of both wild-type SARS-CoV-2 and the D614G variant. To prevent SARS-CoV-2 infections in the lung, the most vulnerable organ for COVID-19, we develop an inhalable formulation by mixing hACE2-containing NCs with mucoadhesive excipient hyaluronic acid, the latter of which could significantly prolong the retention of NCs in the lung after inhalation. Excitingly, inhalation of our formulation could lead to potent pseudovirus inhibition ability in hACE2-expressing mouse model, without imposing any appreciable side effects. Importantly, our inhalable hACE2-containing NCs in the lyophilized formulation would allow long-term storage, facilitating their future clinical use. Thus, this work may provide an alternative tactic to inhibit SARS-CoV-2 infections even with different mutations, exhibiting great potential for treatment of the ongoing COVID-19 epidemic.

Authors+Show Affiliations

Institute of Functional Nano and Soft Materials, Jiangsu Key Laboratory for Carbon-Based Functional Materials and Devices, Soochow University, Suzhou 215123, China.Institute of Functional Nano and Soft Materials, Jiangsu Key Laboratory for Carbon-Based Functional Materials and Devices, Soochow University, Suzhou 215123, China.Institute of Functional Nano and Soft Materials, Jiangsu Key Laboratory for Carbon-Based Functional Materials and Devices, Soochow University, Suzhou 215123, China.Department of Thoracic Surgery, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai 200433, China.Institute of Functional Nano and Soft Materials, Jiangsu Key Laboratory for Carbon-Based Functional Materials and Devices, Soochow University, Suzhou 215123, China.Institute of Functional Nano and Soft Materials, Jiangsu Key Laboratory for Carbon-Based Functional Materials and Devices, Soochow University, Suzhou 215123, China.Institute of Functional Nano and Soft Materials, Jiangsu Key Laboratory for Carbon-Based Functional Materials and Devices, Soochow University, Suzhou 215123, China.Institute of Functional Nano and Soft Materials, Jiangsu Key Laboratory for Carbon-Based Functional Materials and Devices, Soochow University, Suzhou 215123, China.Department of Thoracic Surgery, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai 200433, China; zliu@suda.edu.cn chenqian@suda.edu.cn timyangsh@tongji.edu.cn. School of Materials Science and Engineering, Tongji University, Shanghai 201804, China.Institute of Functional Nano and Soft Materials, Jiangsu Key Laboratory for Carbon-Based Functional Materials and Devices, Soochow University, Suzhou 215123, China; zliu@suda.edu.cn chenqian@suda.edu.cn timyangsh@tongji.edu.cn.Institute of Functional Nano and Soft Materials, Jiangsu Key Laboratory for Carbon-Based Functional Materials and Devices, Soochow University, Suzhou 215123, China; zliu@suda.edu.cn chenqian@suda.edu.cn timyangsh@tongji.edu.cn. Macao Institute of Materials Science and Engineering, Macau University of Science and Technology, Taipa 999078, China.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

34292870

Citation

Zhang, Han, et al. "Inhalable Nanocatchers for SARS-CoV-2 Inhibition." Proceedings of the National Academy of Sciences of the United States of America, vol. 118, no. 29, 2021.
Zhang H, Zhu W, Jin Q, et al. Inhalable nanocatchers for SARS-CoV-2 inhibition. Proc Natl Acad Sci U S A. 2021;118(29).
Zhang, H., Zhu, W., Jin, Q., Pan, F., Zhu, J., Liu, Y., Chen, L., Shen, J., Yang, Y., Chen, Q., & Liu, Z. (2021). Inhalable nanocatchers for SARS-CoV-2 inhibition. Proceedings of the National Academy of Sciences of the United States of America, 118(29). https://doi.org/10.1073/pnas.2102957118
Zhang H, et al. Inhalable Nanocatchers for SARS-CoV-2 Inhibition. Proc Natl Acad Sci U S A. 2021 07 20;118(29) PubMed PMID: 34292870.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Inhalable nanocatchers for SARS-CoV-2 inhibition. AU - Zhang,Han, AU - Zhu,Wenjun, AU - Jin,Qiutong, AU - Pan,Feng, AU - Zhu,Jiafei, AU - Liu,Yanbin, AU - Chen,Linfu, AU - Shen,Jingjing, AU - Yang,Yang, AU - Chen,Qian, AU - Liu,Zhuang, Y1 - 2021/07/02/ PY - 2021/7/22/entrez PY - 2021/7/23/pubmed PY - 2021/8/7/medline KW - SARS-CoV-2 KW - hACE2-containing nanocatchers KW - inhalation KW - mucoadhesive KW - virus inhibitor JF - Proceedings of the National Academy of Sciences of the United States of America JO - Proc Natl Acad Sci U S A VL - 118 IS - 29 N2 - The global coronavirus disease 2019 (COVID-19) pandemic, caused by severe acute respiratory syndrome (SARS)-like coronavirus (SARS-CoV-2), presents an urgent health crisis. More recently, an increasing number of mutated strains of SARS-CoV-2 have been identified globally. Such mutations, especially those on the spike glycoprotein to render its higher binding affinity to human angiotensin-converting enzyme II (hACE2) receptors, not only resulted in higher transmission of SARS-CoV-2 but also raised serious concerns regarding the efficacies of vaccines against mutated viruses. Since ACE2 is the virus-binding protein on human cells regardless of viral mutations, we design hACE2-containing nanocatchers (NCs) as the competitor with host cells for virus binding to protect cells from SARS-CoV-2 infection. The hACE2-containing NCs, derived from the cellular membrane of genetically engineered cells stably expressing hACE2, exhibited excellent neutralization ability against pseudoviruses of both wild-type SARS-CoV-2 and the D614G variant. To prevent SARS-CoV-2 infections in the lung, the most vulnerable organ for COVID-19, we develop an inhalable formulation by mixing hACE2-containing NCs with mucoadhesive excipient hyaluronic acid, the latter of which could significantly prolong the retention of NCs in the lung after inhalation. Excitingly, inhalation of our formulation could lead to potent pseudovirus inhibition ability in hACE2-expressing mouse model, without imposing any appreciable side effects. Importantly, our inhalable hACE2-containing NCs in the lyophilized formulation would allow long-term storage, facilitating their future clinical use. Thus, this work may provide an alternative tactic to inhibit SARS-CoV-2 infections even with different mutations, exhibiting great potential for treatment of the ongoing COVID-19 epidemic. SN - 1091-6490 UR - https://www.unboundmedicine.com/medline/citation/34292870/Inhalable_nanocatchers_for_SARS-CoV-2_inhibition. L2 - http://www.pnas.org/cgi/pmidlookup?view=long&pmid=34292870 DB - PRIME DP - Unbound Medicine ER -