SARS-CoV-2 Infection Depends on Cellular Heparan Sulfate and ACE2.

BioRxiv : the Preprint Server for Biology
Thomas Mandel ClausenJeffrey D Esko

Abstract

We show that SARS-CoV-2 spike protein interacts with cell surface heparan sulfate and angiotensin converting enzyme 2 (ACE2) through its Receptor Binding Domain. Docking studies suggest a putative heparin/heparan sulfate-binding site adjacent to the domain that binds to ACE2. In vitro, binding of ACE2 and heparin to spike protein ectodomains occurs independently and a ternary complex can be generated using heparin as a template. Contrary to studies with purified components, spike protein binding to heparan sulfate and ACE2 on cells occurs codependently. Unfractionated heparin, non-anticoagulant heparin, treatment with heparin lyases, and purified lung heparan sulfate potently block spike protein binding and infection by spike protein-pseudotyped virus and SARS-CoV-2 virus. These findings support a model for SARS-CoV-2 infection in which viral attachment and infection involves formation of a complex between heparan sulfate and ACE2. Manipulation of heparan sulfate or inhibition of viral adhesion by exogenous heparin may represent new therapeutic opportunities.

Citations

Sep 14, 2020·Thrombosis and Haemostasis·Ludovic DrouetGiangiacomo Torri
Nov 27, 2020·Journal of Clinical Medicine·Jay TrivediSiddappa N Byrareddy
Feb 17, 2021·Environmental Science and Pollution Research International·Amr El-SayedMohamed Kamel
Mar 12, 2021·Frontiers in Immunology·Patricia P WadowskiRenate Koppensteiner
Jun 3, 2021·Antioxidants·Alessio Danilo InchingoloFrancesco Inchingolo
Jun 3, 2021·International Journal of Molecular Sciences·Anett HudákTamás Letoha

Datasets Mentioned

BETA
GTX632604
GTX135357
MN908947.3
MN975262.1

Methods Mentioned

BETA
flow cytometry
sulfotransferases
fluorescence
transfection
size exclusion chromatography
Protein Assay
electrophoresis
Infrared Imaging
ICE

Related Concepts

Related Feeds

Adhesion Molecules in Health and Disease

Cell adhesion molecules are a subset of cell adhesion proteins located on the cell surface involved in binding with other cells or with the extracellular matrix in the process called cell adhesion. In essence, cell adhesion molecules help cells stick to each other and to their surroundings. Cell adhesion is a crucial component in maintaining tissue structure and function. Discover the latest research on adhesion molecule and their role in health and disease here.

BioRxiv & MedRxiv Preprints

BioRxiv and MedRxiv are the preprint servers for biology and health sciences respectively, operated by Cold Spring Harbor Laboratory. Here are the latest preprint articles (which are not peer-reviewed) from BioRxiv and MedRxiv.

Related Papers

BioRxiv : the Preprint Server for Biology
T. M. ClausenJeffrey D Esko
Upsala Journal of Medical Sciences
U Lindahl
Annals of the New York Academy of Sciences
U LindahlL G Oscarsson
© 2021 Meta ULC. All rights reserved