Researchers identify a new protein that enables SARS-CoV-2 access into cells

A team of researchers from the Boston University School of Medicine (BUSM) has identified extracellular vimentin as an attachment factor that facilitates SARS-CoV-2 entry into human cells. Vimentin is a structural protein that is widely expressed in the cells of mesenchymal origin such as endothelial cells and a potential novel target against SARS-CoV-2, which could block the infection of the SARS-CoV-2.

"Severe endothelial injury, vascular thrombosis, and obstruction of alveolar capillaries (tiny air sacs scattered throughout the lungs) are common features of severe COVID-19. Identification of vimentin as a host attachment factor for SARS-CoV-2 can provide new insight into the mechanism of SARS-CoV-2 infection of the vascular system and can lead to the development of novel treatment strategies," said corresponding author Nader Rahimi, PhD, associate professor of pathology & laboratory medicine at BUSM.

The researchers used liquid chromatography-tandem mass spectrometry (LC-MS/MS) and identified vimentin as a protein that binds to the SARS-CoV-2 spike (S) protein and facilitates SARS-CoV-2 infection. They also found that depletion of vimentin significantly reduces SARS-CoV-2 infection of human endothelial cells. In contrast, over-expression of vimentin with ACE2 significantly increased the infection rate. "More importantly, we saw that the CR3022 antibody inhibited the binding of vimentin with CoV-2-S-protein, and neutralized SARS-CoV-2 entry into human cells," explained Rahimi.

Collaborators from BUSM included Elke Mühlberger, PhD, Vipul Chitalia, MD, PhD and Catherine E. Costello, PhD.

These findings appear online in the Proceedings of the National Academy of Sciences.

This research was supported in part through a grant from BUSM Genome Science Institute and ARC-COVID-19 (NR and CEC); NIH grants R24 GM134210 and S10 OD021728 (to CEC), funding from BUSM COVID-19 ARC (to CEC and NR) and BUSM Clinical & Translational Science Institute awards from NIH NCATS grant UL1TR001430 (to EM and CEC). Fast Grants (EM), the Evergrande COVID-19 Response Fund Award from the Massachusetts Consortium on Pathogen Readiness (EM and AGS). NIH R01 AI146779 (AGS) and NIGMS T32 GM007753 (AGS).