Decoy nanoparticles protect against COVID-19 by concurrently adsorbing viruses and inflammatory cytokines

Proc Natl Acad Sci U S A. 2020 Nov 3;117(44):27141-27147. doi: 10.1073/pnas.2014352117. Epub 2020 Oct 6.

Abstract

The COVID-19 pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has highlighted the urgent need to rapidly develop therapeutic strategies for such emerging viruses without effective vaccines or drugs. Here, we report a decoy nanoparticle against COVID-19 through a powerful two-step neutralization approach: virus neutralization in the first step followed by cytokine neutralization in the second step. The nanodecoy, made by fusing cellular membrane nanovesicles derived from human monocytes and genetically engineered cells stably expressing angiotensin converting enzyme II (ACE2) receptors, possesses an antigenic exterior the same as source cells. By competing with host cells for virus binding, these nanodecoys effectively protect host cells from the infection of pseudoviruses and authentic SARS-CoV-2. Moreover, relying on abundant cytokine receptors on the surface, the nanodecoys efficiently bind and neutralize inflammatory cytokines including interleukin 6 (IL-6) and granulocyte-macrophage colony-stimulating factor (GM-CSF), and significantly suppress immune disorder and lung injury in an acute pneumonia mouse model. Our work presents a simple, safe, and robust antiviral nanotechnology for ongoing COVID-19 and future potential epidemics.

Keywords: COVID-19; SARS-CoV-2; cell membrane vesicle; cytokine storm; nanodecoy.

Publication types

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

MeSH terms

  • Angiotensin-Converting Enzyme 2
  • Animals
  • Betacoronavirus
  • COVID-19
  • Cell Membrane / chemistry
  • Coronavirus Infections / therapy*
  • Cytokines / antagonists & inhibitors*
  • Granulocyte-Macrophage Colony-Stimulating Factor / antagonists & inhibitors
  • HEK293 Cells
  • Humans
  • Interleukin-6 / antagonists & inhibitors
  • Mice
  • Mice, Inbred ICR
  • Monocytes
  • Nanoparticles / chemistry
  • Nanoparticles / therapeutic use*
  • Pandemics
  • Peptidyl-Dipeptidase A / metabolism
  • Pneumonia, Viral / therapy*
  • Receptors, Cytokine / metabolism
  • SARS-CoV-2
  • THP-1 Cells
  • Virus Internalization / drug effects*

Substances

  • Cytokines
  • Interleukin-6
  • Receptors, Cytokine
  • Granulocyte-Macrophage Colony-Stimulating Factor
  • Peptidyl-Dipeptidase A
  • ACE2 protein, human
  • Ace2 protein, mouse
  • Angiotensin-Converting Enzyme 2