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

Nat Nanotechnol. 2021 Aug;16(8):942-951. doi: 10.1038/s41565-021-00923-2. Epub 2021 Jun 17.

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Administration, Inhalation
  • Angiotensin-Converting Enzyme 2 / metabolism
  • Animals
  • COVID-19 / drug therapy*
  • COVID-19 / virology
  • Cell-Derived Microparticles / metabolism
  • Cell-Derived Microparticles / transplantation
  • Disease Models, Animal
  • Humans
  • Lung Injury / prevention & control*
  • Lung Injury / virology
  • Macaca fascicularis
  • Mice
  • Nanostructures / administration & dosage*
  • Protein Binding
  • SARS-CoV-2 / drug effects*
  • SARS-CoV-2 / metabolism
  • Spheroids, Cellular / metabolism
  • Spike Glycoprotein, Coronavirus / metabolism
  • Viral Load / drug effects

Substances

  • Spike Glycoprotein, Coronavirus
  • spike protein, SARS-CoV-2
  • ACE2 protein, human
  • Angiotensin-Converting Enzyme 2

Supplementary concepts

  • COVID-19 drug treatment