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Pannexin-1 channel opening is critical for COVID-19 pathogenesis #MMPMID34841222
Luu R; Valdebenito S; Scemes E; Cibelli A; Spray DC; Rovegno M; Tichauer J; Cottignies-Calamarte A; Rosenberg A; Capron C; Belouzard S; Dubuisson J; Annane D; de la Grandmaison GL; Cramer-Borde E; Bomsel M; Eugenin E
iScience 2021[Dec]; 24 (12): 103478 PMID34841222show ga
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) rapidly rampaged worldwide, causing a pandemic of coronavirus disease (COVID -19), but the biology of SARS-CoV-2 remains under investigation. We demonstrate that both SARS-CoV-2 spike protein and human coronavirus 229E (hCoV-229E) or its purified S protein, one of the main viruses responsible for the common cold, induce the transient opening of Pannexin-1 (Panx-1) channels in human lung epithelial cells. However, the Panx-1 channel opening induced by SARS-CoV-2 is greater and more prolonged than hCoV-229E/S protein, resulting in an enhanced ATP, PGE(2), and IL-1beta release. Analysis of lung lavages and tissues indicate that Panx-1 mRNA expression is associated with increased ATP, PGE(2), and IL-1beta levels. Panx-1 channel opening induced by SARS-CoV-2 spike protein is angiotensin-converting enzyme 2 (ACE-2), endocytosis, and furin dependent. Overall, we demonstrated that Panx-1 channel is a critical contributor to SARS-CoV-2 infection and should be considered as an alternative therapy.