Cell-mimicking nanodecoys neutralize SARS-CoV-2 and mitigate lung injury in a non-human primate model of COVID-19

• Published in: Nature nanotechnology Vol. 16; no. 8; pp. 942 - 951
• Main Authors: 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
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 01.08.2021; Nature Publishing Group
• Subjects: 631/61/350/2093; 631/61/54/152; ACE2; Administration, Inhalation; Angiotensin; Angiotensin-converting enzyme 2; Angiotensin-Converting Enzyme 2 - metabolism; Animal models; Animals; Antiviral drugs; Cell membranes; Cell-Derived Microparticles - metabolism; Cell-Derived Microparticles - transplantation; Chemical compounds; Chemistry and Materials Science; Conversion; Coronaviruses; COVID-19; COVID-19 - virology; COVID-19 Drug Treatment; Disease Models, Animal; Enzymes; Humans; Inhalation; Injury prevention; Lung Injury - prevention & control; Lung Injury - virology; Lungs; Macaca fascicularis; Materials Science; Mice; Mimicry; Nanostructures - administration & dosage; Nanotechnology; Nanotechnology and Microengineering; Pandemics; Pathogenesis; Peptidyl-dipeptidase A; Pharmacology; Primates; Protein Binding; Respiration; SARS-CoV-2 - drug effects; SARS-CoV-2 - metabolism; Severe acute respiratory syndrome coronavirus 2; Spheroids, Cellular - metabolism; Spike Glycoprotein, Coronavirus - metabolism; Spike protein; Toxicity; Viral diseases; Viral Load - drug effects
• ISSN: 1748-3387; 1748-3395; 1748-3395
• DOI: 10.1038/s41565-021-00923-2

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. In this paper the authors show that nanovesicles coated with lung spheroid cell membranes expressing angiotensin-converting enzyme 2 can bind the spike protein of SARS-CoV-2, neutralizing the virus and preventing lung cell infections in murine and non-human primate models. The nanodecoys could represent a potential therapeutic agent to treat COVID-19.