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

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, Jennifer M Schwarz, Robert Bucki, Alison E. Patteson

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish (US)
JournalSmall
DOIs
StateAccepted/In press - 2021

Keywords

  • cell membranes
  • endocytosis
  • extracellular vimentin
  • pseudoviruses
  • SARS-CoV2
  • spike proteins

ASJC Scopus subject areas

  • Biotechnology
  • Biomaterials
  • Chemistry(all)
  • Materials Science(all)

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