Surface Glycan Modification of Cellular Nanosponges to Promote SARS-CoV-2 Inhibition

J Am Chem Soc. 2021 Oct 27;143(42):17615-17621. doi: 10.1021/jacs.1c07798. Epub 2021 Oct 14.

Abstract

Cellular binding and entry of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are mediated by its spike glycoprotein (S protein), which binds with not only the human angiotensin-converting enzyme 2 (ACE2) receptor but also glycosaminoglycans such as heparin. Cell membrane-coated nanoparticles ("cellular nanosponges") mimic the host cells to attract and neutralize SARS-CoV-2 through natural cellular receptors, leading to a broad-spectrum antiviral strategy. Herein, we show that increasing surface heparin density on the cellular nanosponges can promote their inhibition against SARS-CoV-2. Specifically, cellular nanosponges are made with azido-expressing host cell membranes followed by conjugating heparin to the nanosponge surfaces. Cellular nanosponges with a higher heparin density have a larger binding capacity with viral S proteins and a significantly higher inhibition efficacy against SARS-CoV-2 infectivity. Overall, surface glycan engineering of host-mimicking cellular nanosponges is a facile method to enhance SARS-CoV-2 inhibition. This approach can be readily generalized to promote the inhibition of other glycan-dependent viruses.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • COVID-19 / virology
  • COVID-19 Drug Treatment*
  • Heparin / administration & dosage*
  • Heparin / metabolism
  • Humans
  • Nanostructures / therapeutic use*
  • Polysaccharides / administration & dosage*
  • Polysaccharides / metabolism
  • SARS-CoV-2 / metabolism*

Substances

  • Polysaccharides
  • Heparin