Extracellular Vimentin as a Target Against SARS-CoV-2 Host Cell Invasion.

Abstract

Infection of human cells by pathogens, including SARS-CoV-2, typically proceeds by cell surface binding to a crucial receptor. The primary receptor for SARS-CoV-2 is the angiotensin-converting enzyme 2 (ACE2), yet new studies reveal the importance of additional extracellular co-receptors that mediate binding and host cell invasion by SARS-CoV-2. Vimentin is an intermediate filament protein that is increasingly recognized as being present on the extracellular surface of a subset of cell types, where it can bind to and facilitate pathogens' cellular uptake. Biophysical and cell infection studies are done to determine whether vimentin might bind SARS-CoV-2 and facilitate its uptake. Dynamic light scattering shows that vimentin binds to pseudovirus coated with the SARS-CoV-2 spike protein, and antibodies against vimentin block in vitro SARS-CoV-2 pseudovirus infection of ACE2-expressing cells. The results are consistent with a model in which extracellular vimentin acts as a co-receptor for SARS-CoV-2 spike protein with a binding affinity less than that of the spike protein with ACE2. Extracellular vimentin may thus serve as a critical component of the SARS-CoV-2 spike protein-ACE2 complex in mediating SARS-CoV-2 cell entry, and vimentin-targeting agents may yield new therapeutic strategies for preventing and slowing SARS-CoV-2 infection.

• Authors: Łukasz Suprewicz, Maxx Swoger, Sarthak Gupta, Ewelina Piktel, Fitzroy J Byfield, Daniel V Iwamoto, Danielle Germann, Joanna Reszeć, Natalia Marcińczyk, Robert J Carroll, Paul A Janmey, J M Schwarz, Robert Bucki, Alison E Patteson
• Journal: Small (Weinheim an der Bergstrasse, Germany) (Small) Vol. 18 Issue 6 Pg. e2105640 (02 2022) ISSN: 1613-6829 [Electronic] Germany
• PMID: 34866333 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, Non-P.H.S.)
• Copyright: © 2021 Wiley-VCH GmbH.

Chemical References

• Antibodies
• Spike Glycoprotein, Coronavirus
• Vimentin
• spike protein, SARS-CoV-2

Topics

• Antibodies (pharmacology)
• COVID-19
• Humans
• Protein Binding
• SARS-CoV-2
• Spike Glycoprotein, Coronavirus
• Vimentin (antagonists & inhibitors, metabolism)