Integrin/TGF-β1 inhibitor GLPG-0187 blocks SARS-CoV-2 Delta and Omicron pseudovirus infection of airway epithelial cells which could attenuate disease severity

• DOI: 10.1101/2022.01.02.22268641
• Publication Date: 2022-01-03T17:27:44Z
• Authors: Kelsey E. Huntington; Lindsey Carlsen; Eui-Young So; Matthias Piesche; Olin Liang; Wafik S. El-Deiry
• Keywords: 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 activate TGF-β signaling, we compared plasma levels active total COVID-19+ patients. Plasma TGF-β1 correlated age, race, number medications upon presentation COVID-19, but not sex. Total activated levels. In our preclinical studies, lower lung efficiently Moreover, integrin signaling prevents infectivity, may mitigate severity through decreased activation. This therapeutic strategy be further explored clinical testing unvaccinated populations.