Vimentin binds to SARS-2 spike protein and antibodies targeting extracellular vimentin block uptake of SARS-2 virus-like particles*

The infection of human cells by pathogens, including SARS-CoV-2, typically proceeds by cell surface binding to a crucial receptor. In the case of SARS-CoV-2, angiotensin-converting enzyme 2 (ACE2) has been identified as a necessary but not solely sufficient receptor, suggesting other extracellular factors are involved in 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 cells, where it can bind to and facilitate pathogens’ cellular uptake. Here, we present evidence that extracellular vimentin might acts as a critical component of the SARS-CoV-2 spike protein-ACE2 complex in mediating SARS-2 cell entry. We demonstrate direct binding between vimentin and pseudovirions bearing the SARS-2 spike protein and show that antibodies against vimentin block infection by these viral particles. Our results suggest new therapeutic strategies for preventing and slowing SARS-CoV-2 infection, focusing on targeting cell host surface vimentin.