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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.