Heparan sulfates from bat and human lung and their binding to the spike protein of SARS-CoV-2 virus

Carbohydr Polym. 2021 May 15;260:117797. doi: 10.1016/j.carbpol.2021.117797. Epub 2021 Feb 14.

Abstract

Severe acute respiratory syndrome-related coronavirus-2 (SARS-CoV-2) has resulted in a pandemic and continues to spread at an unprecedented rate around the world. Although a vaccine has recently been approved, there are currently few effective therapeutics to fight its associated disease in humans, COVID-19. SARS-CoV-2 and the related severe acute respiratory syndrome (SARS-CoV-1), and Middle East respiratory syndrome (MERS-CoV) result from zoonotic respiratory viruses that have bats as the primary host and an as yet unknown secondary host. While each of these viruses has different protein-based cell-surface receptors, each rely on the glycosaminoglycan, heparan sulfate as a co-receptor. In this study we compare, for the first time, differences and similarities in the structure of heparan sulfate in human and bat lungs. Furthermore, we show that the spike glycoprotein of COVID-19 binds 3.5 times stronger to human lung heparan sulfate than bat lung heparan sulfate.

Keywords: Disaccharide composition; Heparan sulfate; Molecular weight; SARS-CoV-2 virus; Spike protein RBD.

MeSH terms

  • Animals
  • Chiroptera
  • Female
  • Heparitin Sulfate / chemistry
  • Heparitin Sulfate / isolation & purification
  • Heparitin Sulfate / metabolism*
  • Humans
  • Lung / chemistry*
  • Male
  • Molecular Structure
  • Molecular Weight
  • Protein Binding
  • Receptors, Virus / chemistry
  • Receptors, Virus / isolation & purification
  • Receptors, Virus / metabolism*
  • SARS-CoV-2 / chemistry*
  • Spike Glycoprotein, Coronavirus / metabolism*

Substances

  • Receptors, Virus
  • Spike Glycoprotein, Coronavirus
  • spike protein, SARS-CoV-2
  • Heparitin Sulfate