The current coronavirus disease 2019 (COVID-19) pandemic presents a global public health challenge. The viral pathogen responsible, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), binds to the host receptor ACE2 through its spike (S) glycoprotein, which mediates membrane fusion and viral entry. Although the role of ACE2 as a receptor for SARS-CoV-2 is clear, studies have shown that ACE2 expression is extremely low in various human tissues, especially in the respiratory tract. Thus, other host receptors and/or co-receptors that promote the entry of SARS-CoV-2 into cells of the respiratory system may exist. In this study, we found that the tyrosine-protein kinase receptor UFO (AXL) specifically interacts with the N-terminal domain of SARS-CoV-2 S. Using both a SARS-CoV-2 virus pseudotype and authentic SARS-CoV-2, we found that overexpression of AXL in HEK293T cells promotes SARS-CoV-2 entry as efficiently as overexpression of ACE2, while knocking out AXL significantly reduces SARS-CoV-2 infection in H1299 pulmonary cells and in human primary lung epithelial cells. Soluble human recombinant AXL blocks SARS-CoV-2 infection in cells expressing high levels of AXL. The AXL expression level is well correlated with SARS-CoV-2 S level in bronchoalveolar lavage fluid cells from COVID-19 patients. Taken together, our findings suggest that AXL is a novel candidate receptor for SARS-CoV-2 which may play an important role in promoting viral infection of the human respiratory system and indicate that it is a potential target for future clinical intervention strategies.
【저자키워드】 Molecular biology, Cell Biology, 【초록키워드】 COVID-19, coronavirus disease, SARS-CoV-2, viral infection, ACE2, coronavirus, pandemic, SARS-COV-2 infection, SARS-CoV-2 virus, Intervention, viral entry, Bronchoalveolar lavage fluid, pseudotype, membrane fusion, Respiratory system, glycoprotein, respiratory tract, receptor, ACE2 expression, Lung epithelial cells, COVID-19 patients, N-terminal domain, acute respiratory syndrome, expression level, global public health, host receptor, SARS-CoV-2 entry, human tissues, SARS-CoV-2 S, overexpression, viral pathogen, block, Cell, bind, shown, responsible, significantly, correlated, interact, promote, reduce, expressing, entry of SARS-CoV-2, H1299, HEK293T cell, 【제목키워드】 SARS-CoV-2, Infection, receptor, promote, bronchial epithelial cell,