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Cell-mimicking nanodecoys neutralize SARS-CoV-2 and mitigate lung injury in a non-human primate model of COVID-19.
Li, Zhenhua; Wang, Zhenzhen; Dinh, Phuong-Uyen C; Zhu, Dashuai; Popowski, Kristen D; Lutz, Halle; Hu, Shiqi; Lewis, Mark G; Cook, Anthony; Andersen, Hanne; Greenhouse, Jack; Pessaint, Laurent; Lobo, Leonard J; Cheng, Ke.
  • Li Z; Department of Molecular Biomedical Sciences and Comparative Medicine Institute, North Carolina State University, Raleigh, NC, USA.
  • Wang Z; Joint Department of Biomedical Engineering, The University of North Carolina at Chapel Hill and North Carolina State University, Chapel Hill, NC, USA.
  • Dinh PC; Department of Molecular Biomedical Sciences and Comparative Medicine Institute, North Carolina State University, Raleigh, NC, USA.
  • Zhu D; Joint Department of Biomedical Engineering, The University of North Carolina at Chapel Hill and North Carolina State University, Chapel Hill, NC, USA.
  • Popowski KD; Department of Molecular Biomedical Sciences and Comparative Medicine Institute, North Carolina State University, Raleigh, NC, USA.
  • Lutz H; Joint Department of Biomedical Engineering, The University of North Carolina at Chapel Hill and North Carolina State University, Chapel Hill, NC, USA.
  • Hu S; BreStem Therapeutics Inc., Raleigh, NC, USA.
  • Lewis MG; Department of Molecular Biomedical Sciences and Comparative Medicine Institute, North Carolina State University, Raleigh, NC, USA.
  • Cook A; Joint Department of Biomedical Engineering, The University of North Carolina at Chapel Hill and North Carolina State University, Chapel Hill, NC, USA.
  • Andersen H; Department of Molecular Biomedical Sciences and Comparative Medicine Institute, North Carolina State University, Raleigh, NC, USA.
  • Greenhouse J; Joint Department of Biomedical Engineering, The University of North Carolina at Chapel Hill and North Carolina State University, Chapel Hill, NC, USA.
  • Pessaint L; Department of Molecular Biomedical Sciences and Comparative Medicine Institute, North Carolina State University, Raleigh, NC, USA.
  • Lobo LJ; Joint Department of Biomedical Engineering, The University of North Carolina at Chapel Hill and North Carolina State University, Chapel Hill, NC, USA.
  • Cheng K; Department of Molecular Biomedical Sciences and Comparative Medicine Institute, North Carolina State University, Raleigh, NC, USA.
Nat Nanotechnol ; 16(8): 942-951, 2021 08.
Article in English | MEDLINE | ID: covidwho-1275929
ABSTRACT
Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has grown into a global pandemic, and only a few antiviral treatments have been approved to date. Angiotensin-converting enzyme 2 (ACE2) plays a fundamental role in SARS-CoV-2 pathogenesis because it allows viral entry into host cells. Here we show that ACE2 nanodecoys derived from human lung spheroid cells (LSCs) can bind and neutralize SARS-CoV-2 and protect the host lung cells from infection. In mice, these LSC-nanodecoys were delivered via inhalation therapy and resided in the lungs for over 72 h post-delivery. Furthermore, inhalation of the LSC-nanodecoys accelerated clearance of SARS-CoV-2 mimics from the lungs, with no observed toxicity. In cynomolgus macaques challenged with live SARS-CoV-2, four doses of these nanodecoys delivered by inhalation promoted viral clearance and reduced lung injury. Our results suggest that LSC-nanodecoys can serve as a potential therapeutic agent for treating COVID-19.
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Full text: Available Collection: International databases Database: MEDLINE Main subject: Nanostructures / Lung Injury / SARS-CoV-2 / COVID-19 Drug Treatment Limits: Animals / Humans Language: English Journal: Nat Nanotechnol Year: 2021 Document Type: Article Affiliation country: S41565-021-00923-2

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Full text: Available Collection: International databases Database: MEDLINE Main subject: Nanostructures / Lung Injury / SARS-CoV-2 / COVID-19 Drug Treatment Limits: Animals / Humans Language: English Journal: Nat Nanotechnol Year: 2021 Document Type: Article Affiliation country: S41565-021-00923-2