RT Journal Article SR Electronic T1 CD209L/L-SIGN and CD209/DC-SIGN act as receptors for SARS-CoV-2 and are differentially expressed in lung and kidney epithelial and endothelial cells JF bioRxiv FD Cold Spring Harbor Laboratory SP 2020.06.22.165803 DO 10.1101/2020.06.22.165803 A1 Amraie, Razie A1 Napoleon, Marc A. A1 Yin, Wenqing A1 Berrigan, Jacob A1 Suder, Ellen A1 Zhao, Grace A1 Olejnik, Judith A1 Gummuluru, Suryaram A1 Muhlberger, Elke A1 Chitalia, Vipul A1 Rahimi, Nader YR 2020 UL http://biorxiv.org/content/early/2020/06/23/2020.06.22.165803.abstract AB The spike protein (S) of SARS-CoV-2 mediates entry into human cells by interacting with human angiotensin-converting enzyme 2 (ACE2) through its receptor-binding domain (RBD). Here, we report identification of CD209L/L-SIGN and a related protein, CD209/DSIGN as alternative receptors capable of mediating SARS-CoV-2 entry into human cells. Immunofluorescence staining of human tissues revealed a prominent expression of CD209L in the lung and kidney epithelial and endothelial cells of small and medium-sized vessels, whereas CD209 was detected only in a limited number of cell types. Biochemical assays revealed that ectopically expressed CD209L and CD209 bind to S-RBD and mediate SARS-CoV-2 S-pseudotyped virus entry. Furthermore, we demonstrate that human endothelial cells endogenously express CD209L and are permissive to SARS-CoV-2 infection. Soluble CD209L-Fc neutralized virus entry. Our observations show that CD209L and CD209 serve as alternative receptors for SARS-CoV-2 in disease-relevant cell types, including the vascular system. This may have implications for antiviral drug development.Competing Interest StatementThe authors have declared no competing interest.