Abstract TP314: The α5 Integrin Inhibitor ATN161 Mitigates SARS-CoV-2- Induced Brain Endothelial Barrier Disruption and Neuroinflammation α5 Integrin Inhibitor ATN 161

• DOI: 10.1161/str.55.suppl_1.tp314
• Publication Date: 2024-02-01T10:11:28Z
• Authors: Meenakshi Umar; Narayanappa Amruta; Timothy E Gressett; Milla Volic; Blake Ouvrier; Saifudeen Ismael; Grant Talkington; Gregory J Bix
• Keywords: 03 medical and health sciences; 0302 clinical medicine

Introduction: Although SARS-CoV-2 infection can cause a wide range of mild to severe symptoms, the pathophysiology acute and long-term neurological manifestations remains elusive. The arginine-glycine-aspartic acid motif viral spike protein may use bind integrins receptors in CNS, which play an important role cerebrovascular integrity. Here we investigate integrin α5β1 mediating brain endothelial damage inflammation during infection. Method: Mouse microvascular cells (bEnd.3) were treated with (Isolate USA-WA1/2020) or delta variant for 24h then later exposed hypoxia 6h (to model effects vivo pulmonary infection). Cells pretreated ATN-16, 1h before challenge. Further, BALB/c mice inoculated intranasally 2x10 4 -PFU MA-10 strain 1mg/kg ATN-161, inhibitor, retro-orbitally. brains collected 3 days post-infection neuropathological evaluation. Results: inoculations induced α5 decreased claudin-5 expression bEnd.3 dose-dependent manner. challenge at 0.5 μg followed by resulted increased either SARS-CoV-2+hypoxia combination. ATN-161 (10μM) pretreatment inhibited SARS-CoV-2+hypoxia-induced upregulation restored loss cells. studies showed significant increase pro-inflammatory response as measured cytokine IL-6 decrease barrier integrity tight junction MA10-infected compared mock controls. treatment claudin 5 infected mice. Conclusion: Therefore, propose that targeting through inhibitors such offers promising therapeutic strategy attenuating its immunological impact on vasculature. This approach be pivotal reducing both chronic morbidities associated COVID-19.