Integrin/TGF-β1 Inhibitor GLPG-0187 Blocks SARS-CoV-2 Delta and Omicron Pseudovirus Infection of Airway Epithelial Cells In Vitro, Which Could Attenuate Disease Severity

• DOI: 10.3390/ph15050618
• Publication Date: 2022-05-17T12:34:29Z
• Authors: Kelsey E. Huntington; Lindsey Carlsen; Eui-Young So; Matthias Piesche; Olin Liang; Wafik S. El-Deiry
• Keywords: RS1-441; Pharmacy and materia medica; integrin; SARS-CoV-2; TGF-β1; R; HSAE; GLPG-0187; integrin; MEKi; SARS-CoV-2; TGF-β1; ACE2; COVID-19; Omicron; Delta; Medicine; MEKi; GLPG-0187; HSAE; Article; 3. Good health

As COVID-19 continues to pose major risk for vulnerable populations, including the elderly, immunocompromised, patients with cancer, and those contraindications vaccination, novel treatment strategies are urgently needed. SARS-CoV-2 infects target cells via RGD-binding integrins, either independently or as a co-receptor surface receptor angiotensin-converting enzyme 2 (ACE2). We used pan-integrin inhibitor GLPG-0187 demonstrate blockade of pseudovirus infection cells. Omicron infected normal human small airway epithelial (HSAE) significantly less than D614G Delta variant pseudovirus, effectively blocked in dose-dependent manner across multiple viral variants. inhibited HSAE more other Pre-treatment MEK (MEKi) VS-6766 enhanced inhibition by GLPG-0187. Because integrins activate transforming growth factor beta (TGF-β) signaling, we compared plasma levels active total TGF-β COVID-19+ patients. The TGF-β1 correlated age, race, number medications upon presentation COVID-19, but not sex. Total activated levels. Moreover, integrin signaling prevents infectivity, it may mitigate severity through decreased activation. This therapeutic strategy be further explored clinical testing unvaccinated populations.