التفاصيل البيبلوغرافية
| العنوان: |
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. |
| المؤلفون: |
Huntington, Kelsey E.1,2,3,4,5 (AUTHOR) eui_young_so@brown.edu, Carlsen, Lindsey1,2,3,4,5 (AUTHOR) lindsey_carlsen@brown.edu, So, Eui-Young3,4,6 (AUTHOR), Piesche, Matthias7,8 (AUTHOR) matthias.piesche@googlemail.com, Liang, Olin3,4,6 (AUTHOR), El-Deiry, Wafik S.1,2,3,4,5,6 (AUTHOR) matthias.piesche@googlemail.com |
| المصدر: |
Pharmaceuticals (14248247). May2022, Vol. 15 Issue 5, p618-618. 17p. |
| مصطلحات موضوعية: |
*SARS-CoV-2 Omicron variant, *SARS-CoV-2 Delta variant, *TRANSFORMING growth factors-beta, *SARS-CoV-2, *EPITHELIAL cells |
| مستخلص: |
As COVID-19 continues to pose major risk for vulnerable populations, including the elderly, immunocompromised, patients with cancer, and those with contraindications to vaccination, novel treatment strategies are urgently needed. SARS-CoV-2 infects target cells via RGD-binding integrins, either independently or as a co-receptor with surface receptor angiotensin-converting enzyme 2 (ACE2). We used pan-integrin inhibitor GLPG-0187 to demonstrate the blockade of SARS-CoV-2 pseudovirus infection of target cells. Omicron pseudovirus infected normal human small airway epithelial (HSAE) cells significantly less than D614G or Delta variant pseudovirus, and GLPG-0187 effectively blocked SARS-CoV-2 pseudovirus infection in a dose-dependent manner across multiple viral variants. GLPG-0187 inhibited Omicron and Delta pseudovirus infection of HSAE cells more significantly than other variants. Pre-treatment of HSAE cells with MEK inhibitor (MEKi) VS-6766 enhanced the inhibition of pseudovirus infection by GLPG-0187. Because integrins activate transforming growth factor beta (TGF-β) signaling, we compared the plasma levels of active and total TGF-β in COVID-19+ patients. The plasma TGF-β1 levels correlated with age, race, and number of medications upon presentation with COVID-19, but not with sex. Total plasma TGF-β1 levels correlated with activated TGF-β1 levels. Moreover, the inhibition of integrin signaling prevents SARS-CoV-2 Delta and Omicron pseudovirus infectivity, and it may mitigate COVID-19 severity through decreased TGF-β1 activation. This therapeutic strategy may be further explored through clinical testing in vulnerable and unvaccinated populations. [ABSTRACT FROM AUTHOR] |
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