Spike-heparan sulfate interactions in SARS-CoV-2 infection

Fiona L Kearns; Daniel R Sandoval; Lorenzo Casalino; Thomas M Clausen; Mia A Rosenfeld; Charlotte B Spliid; Rommie E Amaro; Jeffrey D Esko

doi:10.1016/j.sbi.2022.102439

Spike-heparan sulfate interactions in SARS-CoV-2 infection

Curr Opin Struct Biol. 2022 Oct:76:102439. doi: 10.1016/j.sbi.2022.102439. Epub 2022 Jul 6.

Authors

Fiona L Kearns¹, Daniel R Sandoval², Lorenzo Casalino³, Thomas M Clausen², Mia A Rosenfeld⁴, Charlotte B Spliid², Rommie E Amaro⁵, Jeffrey D Esko⁶

Affiliations

¹ Department of Chemistry and Biochemistry, University of California, San Diego, La Jolla, CA 92093, USA. Electronic address: https://twitter.com/fiona_chembot.
² Department of Cellular and Molecular Medicine, University of California, San Diego, La Jolla, CA 92093, USA.
³ Department of Chemistry and Biochemistry, University of California, San Diego, La Jolla, CA 92093, USA. Electronic address: https://twitter.com/LCasalino88.
⁴ Department of Chemistry and Biochemistry, University of California, San Diego, La Jolla, CA 92093, USA. Electronic address: https://twitter.com/mia_rosenfeld.
⁵ Department of Chemistry and Biochemistry, University of California, San Diego, La Jolla, CA 92093, USA; Glycobiology Research and Training Center, University of California, San Diego, La Jolla, CA 92093, USA. Electronic address: https://twitter.com/RommieAmaro.
⁶ Department of Cellular and Molecular Medicine, University of California, San Diego, La Jolla, CA 92093, USA; Glycobiology Research and Training Center, University of California, San Diego, La Jolla, CA 92093, USA. Electronic address: jesko@health.ucsd.edu.

Abstract

Recent biochemical, biophysical, and genetic studies have shown that heparan sulfate, a major component of the cellular glycocalyx, participates in infection of SARS-CoV-2 by facilitating the so-called open conformation of the spike protein, which is required for binding to ACE2. This review highlights the involvement of heparan sulfate in the SARS-CoV-2 infection cycle and argues that there is a high degree of coordination between host cell heparan sulfate and asparagine-linked glycans on the spike in enabling ACE2 binding and subsequent infection. The discovery that spike protein binding and infection depends on both viral and host glycans provides insights into the evolution, spread and potential therapies for SARS-CoV-2 and its variants.

Publication types

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

MeSH terms

Angiotensin-Converting Enzyme 2
Asparagine / metabolism
Binding Sites
COVID-19*
Heparitin Sulfate
Humans
Protein Binding
SARS-CoV-2
Spike Glycoprotein, Coronavirus / chemistry
Spike Glycoprotein, Coronavirus / genetics
Spike Glycoprotein, Coronavirus / metabolism

Substances

Spike Glycoprotein, Coronavirus
spike protein, SARS-CoV-2
Asparagine
Heparitin Sulfate
Angiotensin-Converting Enzyme 2

Abstract

Publication types

MeSH terms

Substances

Grants and funding