Molecular docking of SARS-COV-2 Spike epitope sequences identifies heterodimeric peptide-protein complex formation with human Zo-1, TLR8 and brain specific glial proteins

Non-Productive Infection of Glial Cells with SARS-CoV-2 in Hamster Organotypic Cerebellar Slice Cultures

“…Similarly, another gene involved in BBB integrity, N-myc downstream-regulated gene 2 (Ndrg2), that is principally expressed in astrocytes had increased expression at 14 DPI [60]. In silico simulations predict binding of SARS-CoV-2 spike protein to Ndrg2 and further suggests the potential for the triggering of inflammation at the BBB [61].…”

Effects of spike protein and toxin-like peptides found in COVID-19 patients on human 3D neuronal/glial model undergoing differentiation: Possible implications for SARS-CoV-2 impact on brain development

“…Spike protein alone has been shown in one study to induce several damages associated with COVID-19, including damage to the lungs and arteries, inflammation of endothelial cells lining the pulmonary artery walls, together with impairment of mitochondrial function, decrease of ACE2 expression and eNOS activity, and increase of glycolysis as observed in vitro (on endothelial cells treated for 24 h with 4 μg/mL Spike) and in vivo (upon intratracheal administration of a pseudovirus expressing Spike protein to Syrian hamsters) [124] . Spike proteins (S1 and active trimer, 15 and 30 nM) have been found to induce mitochondrial damage in brain endothelial cells [125] , and spike protein epitopes have been shown to interact with human toll-like receptor 8 (TLR 8), brain targeted Vascular Cell adhesion Molecules (VCAM1) proteins, Zonula Occludens (ZO), and some glia specific proteins (i.e., NDRG2 and Apo- S100B), which can lead to neuroinflammation [126] . Moreover, 10 nM SARS-CoV-2 viral spike proteins have been shown to alter BBB functions and induce pro-inflammatory response after 24 h in primary human brain microvascular endothelial cells (hBMVECs) cultured in 2D and 3D [127] .…”

SARS-CoV-2 infection of human brain microvascular endothelial cells leads to inflammatory activation through NF-κB non-canonical pathway and mitochondrial remodeling

“…ZO-1 possesses a PDZ domain, which is responsible for binding and interaction with other proteins (Saras & Heldin, 1996; Giepmans & Moolenaar, 1998). Interestingly, ACE2 possesses a PDZ-binding domain (Dasgupta & Bandyopadhyay, 2021; Caillet-Saguy & Wolff, 2021), and it has been suggested that epitopes of viral proteins, such as 1–60: M1Lys60 and 241–300: Ala240-Glu300 could directly bind to ZO-1 and VCAM-1 PDZ domains, thus suggesting a possible alternative route of CNS entry. We found ZO-1 and claudin-5 protein levels to be increased after 24 h of infection in HBMECs and this increase is consistent with what our group recently demonstrated with S1 treatment (Torices et al, 2021).…”