Physicochemical Nature of SARS-CoV-2 Spike Protein Binding to Human Vimentin

Vimentin, a protein that builds part of the cytoskeletonand isinvolved in many aspects of cellular function, was recently identifiedas a cell surface attachment site for the severe acute respiratorysyndrome coronavirus 2 (SARS-CoV-2). The present study investigatedthe physicochemical nature of the binding between the SARS-CoV-2 S1glycoprotein receptor binding domain (S1 RBD) and human vimentin usingatomic force microscopy and a quartz crystal microbalance. The molecularinteractions of S1 RBD and vimentin proteins were quantified usingvimentin monolayers attached to the cleaved mica or a gold microbalancesensor as well as in its native extracellular form present on thelive cell surface. The presence of specific interactions between vimentinand S1 RBD was also confirmed using in silico studies. This work providesnew evidence that cell-surface vimentin (CSV) functions as a sitefor SARS-CoV-2 virus attachment and is involved in the pathogenesisof Covid-19, providing a potential target for therapeutic countermeasures.