Entering severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) into human cells is an essential step in the transmission of the virus and the onset of COVID-19.
Although pulmonary epithelial cells are the original target, SARS-CoV-2 may also infect endothelial cells. Endothelial cells are the main components of the vascular system and cardiovascular complication is a distinctive sign of severe COVID-19. The angiotensin 2 conversion enzyme (ACE2) is the input receptor of SRAS-CoV-2. However, the possible involvement of other cellular components in viral input is not entirely understood.
A research team from the Boston University School of Medicine (BUSM) has identified extracellular Vimentin as an attachment factor that facilitates the entry of CoV-2 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 and tandem mass spectrometry (LC-MS/MS) and identified Vimentin as a protein that binds to the SARS-CoV-2 transient (S) protein and facilitates SARS-CoV-2 infection.
They also found that the depletion of Vimentin considerably reduces SARS CoV-2 infection in human endothelial cells. On the other hand, the overexpression of vimentin with ACE2 significantly increased the rate of infection.
“Most importantly, we found that the CR3022 antibody inhibited the binding of Vimentin with the CoV-2-S protein and neutralized the entry of SARS-CoV-2 into human cells,” explained Rahimi.
Extracellular vimentin is an attachment factor that facilitates SARS-CoV-2 entry into human endothelial cells – PNAS Article.