Can the SARS-CoV-2 Spike Protein Bind Integrins Independent of the RGD Sequence? – PMC

Vβ₃ and α₅β₁ integrinsnHighlight:changes in integrin expression during SARS-CoV-2 infectionnHighlight:Several integrin-binding motifs are shown to exhibit high sequence similarity with solvent accessible regions of the spike receptor-binding domain.nHighlight:Integrins are an ancient superfamily of heterodimeric transmembrane proteins that are involved in diverse cell processes, such as cell-cell adhesion and both inside-out and outside-in cell signaling, at cell surfacesnHighlight:α_Vβ₃, are ubiquitously expressed across human tissuesnHighlight:Because integrins are largely accessible on the surface of human cells, they are a common target for cell entry by viral pathogens nHighlight:SARS-CoV-2 spike protein directly binds α_Vβ₃ and α₅β₁ integrins and may also interact with α₃, β₁, α₄, and α_X integrin subunits nHighlight:binding to the spike protein, that have been shown to mediate viral entry through the spike proteinnHighlight:Binding assays have shown that the spike protein directly interacts with α₅β₁ and α_Vβ₃ integrinsnHighlight:RGD peptide were found to block the SARS-CoV-2 spike protein from binding to α_Vβ₃ and α₅β₁ integrins, respectively, indicating that the spike protein binds in an RGD-dependent mannernHighlight:increases in expression suggest potential usage, while decreases in expression may rule out their involvementnHighlight:integrin expression may also be an indicator of several other altered cellular processes, such as inflammation and apoptosis, during infectionnHighlight:increased integrin expression has also been shown to enhance viral replication irrespective of binding to viral surface proteins, and decreased expression may result as a viral mechanism to prevent multiple viruses from infecting the same cell or as a defence mechanism by the hostn]]>