Summary 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-1β release. Analysis of lung lavages and tissues indicate that Panx-1 mRNA expression is associated with increased ATP, PGE 2 , and IL-1β 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. Graphical abstract Highlights • Pannexin-1 (Panx-1) is a critical player in COVID-19 lung pathogenesis • SARS-CoV-2 Panx-1 channel opening is ACE-2/furin/endocytosis dependent • SARS-CoV-2-associated Panx-1 channel opening induces inflammation • Blocking Panx-1 channels reduces viral replication and inflammation Cell biology; Molecular physiology; Virology
【저자키워드】 Virology, Cell Biology, Molecular physiology, 【초록키워드】 COVID-19, coronavirus disease, SARS-CoV-2, Inflammation, coronavirus, pandemic, therapy, Pathogenesis, S protein, furin, SARS-COV-2 infection, lung, angiotensin-converting enzyme 2, COVID, ACE-2, Protein, viral replication, SARS-CoV-2 spike protein, human lung, epithelial cells, common cold, ATP, Critical, IL-1β, acute respiratory syndrome, Abstract, tissue, mRNA expression, human coronavirus 229E, blocking, lung lavage, greater, responsible, resulting, virus, demonstrated, induce, reduce, purified, biology of SARS-CoV-2, PGE, 【제목키워드】 COVID-19 pathogenesis, Critical,