While the relationship between the spike protein of SARS-CoV-2 and the angiotensin converting enzyme 2 (ACE2) receptor has been readily established, the S1 subunit also contains a solvent-exposed arginine-glycine-aspartic acid (RGD) binding motif that is predominantly recognized by integrins.
Download Now
SARS-CoV-2, with its higher transmissibility, harbors unique spike protein mutations, like K403R, potentially enhancing integrin-mediated host cell binding, particularly in endothelial cells. Investigating epithelial-to-endothelial transmission and αVβ3 antagonist effects on viral adhesion sheds light on potential therapeutic strategies against SARS-CoV-2 infection.
Accumulating evidence suggests that common sepsis pathogens, including bacteria, fungi, and viruses, all contain a critical integrin recognition motif, Arg-Gly-Asp (RGD), in their major cell wall-exposed proteins that might act as ligands to crosslink to major integrins resulting in systemic dysregulation.
Endothelial-derived exosomes from induce a pro-inflammatory monocyte phenotype via upregulated miR-99, targeting mTOR. Inhibition of miRNAs reverses this effect, highlighting a potential therapeutic avenue against sepsis-induced inflammation.
S. aureus cell wall protein Clumping factor A (ClfA) binds to endothelial cell integrin αVβ3, leading to endothelial barrier disruption and apoptosis. Treatment with the αVβ3 blocker cilengitide significantly inhibits ClfA binding and reduces endothelial dysfunction, suggesting a potential therapeutic approach for sepsis.
E. coli binds to endothelial cells via outer membrane protein A, causing endothelial barrier disruption and apoptosis. Treatment with the αVβ3 antagonist, cilengitide, reduces endothelial dysfunction, suggesting its potential as an early therapeutic intervention for sepsis.
Clengitide is capable of competitively antagonizing bacterial binding to endothelial cells and as a result removes the signal that perpetuates vascular endothelial cell involvement in sepsis, and thus presents as a potential as new complementary strategy for the treatment of established sepsis and as prophylaxis in high risk patients.
Public awareness of sepsis has improved but remains varied globally, with efforts focused on education about its signs and symptoms. Campaigns emphasize the importance of early recognition and prompt medical intervention to prevent severe complications and fatalities. Despite progress, continued efforts are needed to ensure widespread understanding and response to this life-threatening condition.
MicroRNAs regulate gene expression in eukaryotic cells, impacting various physiological processes, including cardiovascular function. Dysregulated microRNA expression is linked to diseases, including infections, with a crucial role in the host response to microbes, especially within the cardiovascular system and innate immune cells.
