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DOI10.1073/pnas.2102957118
Inhalable nanocatchers for SARS-CoV-2 inhibition
Zhang H.; Zhu W.; Jin Q.; Pan F.; Zhu J.; Liu Y.; Chen L.; Shen J.; Yang Y.; Chen Q.; Liu Z.
发表日期2021
ISSN0027-8424
卷号118期号:29
英文摘要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. © 2021 National Academy of Sciences. All rights reserved.
英文关键词HACE2-containing nanocatchers; Inhalation; Mucoadhesive; SARS-CoV-2; Virus inhibitor
语种英语
scopus关键词ACE2 protein, human; adhesive agent; cryoprotective agent; excipient; hyaluronic acid; nanomaterial; animal; chemistry; drug effect; drug storage; epithelium cell; genetics; HEK293 cell line; human; inhalational drug administration; lung; metabolism; mouse; physiology; prevention and control; transgenic mouse; virology; virus attachment; Adhesives; Administration, Inhalation; Angiotensin-Converting Enzyme 2; Animals; COVID-19; Cryoprotective Agents; Drug Storage; Epithelial Cells; Excipients; HEK293 Cells; Humans; Hyaluronic Acid; Lung; Mice; Mice, Transgenic; Nanostructures; SARS-CoV-2; Virus Attachment
来源期刊Proceedings of the National Academy of Sciences of the United States of America
文献类型期刊论文
条目标识符http://gcip.llas.ac.cn/handle/2XKMVOVA/238477
作者单位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; School of Materials Science and Engineering, Tongji University, Shanghai, 201804, China; Macao Institute of Materials Science and Engineering, Macau University of Science and Technology, Taipa, 999078, Macau
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GB/T 7714
Zhang H.,Zhu W.,Jin Q.,et al. Inhalable nanocatchers for SARS-CoV-2 inhibition[J],2021,118(29).
APA Zhang H..,Zhu W..,Jin Q..,Pan F..,Zhu J..,...&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).
MLA Zhang H.,et al."Inhalable nanocatchers for SARS-CoV-2 inhibition".Proceedings of the National Academy of Sciences of the United States of America 118.29(2021).
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