ORCID

Maxx Swoger: 0000-0001-6128-8704

Sarthak Gupta: 0000-0002-3950-7955

Robert Carroll: 0000-0002-0536-9734

Alison E. Patteson: 0000-0002-4004-1734

J. M. Schwarz: 0000-0001-9880-9999

Document Type

Article

Date

Winter 12-5-2021

Language

English

Funder(s)

National Science Foundation, National Institutes of Health, National Science Center of Poland, Syracuse University SOURCE grant

Funding ID

NSF MCB 2032861, NIH R35 GM142963, NIH GM136259, NIH S10 OD026946-01A1, UMO-2020/01/0/NZ6/00082

Acknowledgements

The authors acknowledge Robert Goldman, Karen Ridge, and Nav Singh for insightful discussions. This work was supported by NSF MCB 2032861 award to A.E.P. and J.M.S., NIH R35 GM142963 award to A.E.P., NIH GM136259 award to P.A.J., and the National Science Center of Poland: UMO-2020/01/0/NZ6/00082 awarded to R.B. D.G. acknowledges funding from Syracuse University SOURCE grant. The authors also acknowledge Michael Bates and the Blatt BioImaging Center for use of the LSM 980, which was supported by NIH S10 OD026946-01A1.

Official Citation

Suprewicz, Ł., Swoger, M., Gupta, S., Piktel, E., Byfield, F. J., Iwamoto, D. V., Germann, D., Reszeć, J., Marcińczyk, N., Carroll, R. J., Janmey, P. A., Schwarz, J. M., Bucki, R., Patteson, A. E., Extracellular Vimentin as a Target Against SARS-CoV-2 Host Cell Invasion. Small 2022, 18, 2105640. https://doi.org/10.1002/smll.202105640

Disciplines

Physics

Description/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.

Creative Commons License

Creative Commons Attribution 4.0 International License
This work is licensed under a Creative Commons Attribution 4.0 International License.

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