Endothelial glycocalyx shields the interaction of SARS-CoV-2 spike protein with ACE2 receptors

Abstract

Endothelial cells (ECs) play a crucial role in the development and propagation of the severe COVID-19 stage as well as multiorgan dysfunction. It remains, however, controversial whether COVID-19-induced endothelial injury is caused directly by the infection of ECs with SARS-CoV-2 or via indirect mechanisms. One of the major concerns is raised by the contradictory data supporting or denying the presence of ACE2, the SARS-CoV-2 binding receptor, on the EC surface. Here, we show that primary human pulmonary artery ECs possess ACE2 capable of interaction with the viral Spike protein (S-protein) and demonstrate the crucial role of the endothelial glycocalyx in the regulation of the S-protein binding to ACE2 on ECs. Using force spectroscopy method, we directly measured ACE2- and glycocalyx-dependent adhesive forces between S-protein and ECs and characterized the nanomechanical parameters of the cells exposed to S-protein. We revealed that the intact glycocalyx strongly binds S-protein but screens its interaction with ACE2. Reduction of glycocalyx layer exposes ACE2 receptors and promotes their interaction with S-protein. These results indicate that the susceptibility of ECs to COVID-19 infection may depend on the glycocalyx condition.

Of mice and human-specific long noncoding RNAs

“…The latter cell type has been the focus of numerous studies given the mounting evidence for SARS-CoV-2-induced endotheliopathy, considered an important contributor to the pathogenesis of COVID-19 (Goshua et al 2020 ). The undetectable levels of ACE2 protein in human endothelial cells shown here is consistent with a recent report that failed to detect ACE2 mRNA in several human endothelial cell types (McCracken et al 2021 ), but inconsistent with other reports (Hamming et al 2004 ; Targosz-Korecka et al 2021 ; Wagner et al 2021 ). These disparate findings highlight the ongoing controversy over whether endothelial cells are prone to SARS-CoV-2 infection (Goldsmith et al 2020 ; McCracken et al 2021 ; Targosz-Korecka et al 2021 ; Varga et al 2020 ; Wagner et al 2021 ).…”

Bovine Serum Albumin-Coated Niclosamide-Zein Nanoparticles as Potential Injectable Medicine against COVID-19

“…The smaller size, of around 200 nm, is highly advantageous for the BSA-Zein-NIC NPs, as these nanohybrid drugs can easily enter into the infected cells and eventually induce anti-viral action. In addition, the damaged endothelial glycocalyx [30][31][32] in COVID-19 patients might further enhance a kind of selective uptake of BSA-coated Zein-NIC NPs [29][30][31]43].…”

The SARS-CoV-2 Entry Inhibition Mechanisms of Serine Protease Inhibitors, OM-85, Heparin and Soluble HS Might Be Linked to HS Attachment Sites

“…If based on fact (c), we conclude that “HS chains promotes infections”, how could we justify that the same heparin which is an entry competitive inhibitor of SARS-CoV-2 spontaneously stimulates by 2- to 3-fold the biosynthesis of the cell-layer HS (infection promoter element)? Especially when the pre-incubation of cells with heparin before infection also inhibits the viral attachment of SARS-CoV-2 [ 93 , 94 ]. The pre-incubation of cells with heparin 30 min before infection, as was the case in the Partridge et al [ 93 ] experiment, significantly increases the amount of cell-layer HS (with the same sulfation), and yet viral attachment is inhibited with this pre-treatment, in addition to studies on the effects of desulfation discussed in Section 2 .…”