Abstract
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.
Highlights
Coronavirus disease 2019 (COVID-19) has caused a global pandemic since December 2019 and presents a global public health threat
Recent studies have identified many neutralizing human antibodies that bind to SARS-CoV-2 S but do not bind the RBD.[18,19]. These results indicate that other important host receptors and/or co-receptors might exist that bind to different domain(s) of SARS-CoV-2 S and promote the entry of SARS-CoV-2 into cells of the respiratory system
COVID-19 primarily causes respiratory system illness; an increasing number of case reports on SARS-CoV-2 infection have shown that it can affect almost all of the body’s primary organs, including the lungs, pharynx, heart, liver, brain, and kidneys.[7]
Summary
Coronavirus disease 2019 (COVID-19) has caused a global pandemic since December 2019 and presents a global public health threat. The causative viral pathogen, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is a highly contagious enveloped positive-strand RNA virus[1] that causes upper respiratory diseases, fever and severe pneumonia in humans.[1,2] SARS-CoV-2 belongs to the β coronavirus genus. Other members of this genus include severe acute respiratory syndrome coronavirus (SARS-CoV) and middle east respiratory syndrome coronavirus (MERS-CoV), which caused outbreaks in 2003 and 2012, respectively, though on a much smaller scale.[3,4] SARS-CoV-2 preferentially infects cells of the respiratory tract[5] but has been detected in almost all human organs, including the lungs, pharynx, heart, liver, brain, kidneys and digestive system organs.[6,7,8].
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
