Abstract TMP19: Atn-161 Prevents α5 Integrin-mediated Tight Junction Disruption Caused By Sars-cov-2 And Its Delta Variant In Brain Endothelial Cells

• DOI: 10.1161/str.53.suppl_1.tmp19
• Publication Date: 2022-02-03T10:01:59Z
• Authors: Amruta Narayanappa; William Eskew; Blake Ouvrier; Ifechukwude J Biose; Sophie Hefter; Timothy E Gressett; Pervez Khan; Gregory J Bix
• Keywords: Hypoxia

Patients with significant cerebrovascular comorbidities (e.g. brain ischemia, vascular dementia) are more affected and likely to have worsened post-acute neurologic sequelae after SARS-CoV-2 infection. This may be due viral invasion propagation in endothelial cells (BECs) disruption of the blood-brain barrier (BBB). Viral spike protein used bind infect host encodes an arginine-glycine-aspartic acid (RGD) motif that it use integrins cell receptors play important role integrity. Therefore, represent acute therapeutic target. However, interplay between dysregulation, integrin function, COVID-19 is unclear. As we previously demonstrated activation α5 plays a key BBB breakdown, stroke injury, OGD/R, infection, its inhibition clinically validated peptide ATN-161 these conditions, hypothesize alters BEC (and associated tight junction protein) expression as means infecting altering integrity, this can prevented by ATN-161. Methods: Mouse BECs (bEnd3) were inoculated heat-inactivated (Isolate USA-WA1/2020) or delta variant for 24 h then later exposed hypoxia 6h model effects vivo pulmonary Cells pretreated (1, 5, 10μM) 1h before challenge during hypoxia. claudin-5 proteins analyzed immunoblotting. Results: Both inoculations induced decreased (delta > SARS-CoV-2) dose-dependent fashion, although higher doses (2.5 5 μg) had no effect on proteins. at 0.5 μg followed resulted increased either SARS-CoV-2+hypoxia combination. (10μM) pretreatment inhibited SARS-CoV-2+hypoxia-induced upregulation restored loss. In addition anti-viral effects, therapy SARS-CoV-2-mediated injury.