(Boston)—The entry of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) into human cells is an essential step for virus transmission and development of COVID 19. Although the lung epithelial cells are its initial target, SARS-CoV-2 also can infect endothelial cells. Endothelial cells are the major constituents of the vascular system and cardiovascular complication is a hallmark of severe COVID-19. Angiotensin-converting enzyme 2 (ACE2) is the entry receptor for SARS-CoV-2. However, the possible involvement of other cellular components in the viral entry is not fully understood.
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.
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).
Proceedings of the National Academy of Sciences
Experimental study
Cells
Extracellular vimentin is an attachment factor that facilitates SARS-CoV-2 entry into human endothelial cells
25-Jan-2022