Utilizing this pseudotype system, we screened a panel of human and monkey cell lines for their susceptibility of SARS-CoV-2 S-mediated transduction. In line with SASR-CoV-2 causing respiratory infections in humans, we found that human lung cancer cell line Calu3 is highly susceptible to SARS-CoV-2 S-mediated entry. LLCMK2 cells, a rhesus monkey kidney epithelium cell line, exhibited different susceptibility to SARS-CoV S and SARS-CoV-2 S transduction, but the reasons for this are currently not known and require further investigation. Both S proteins use hACE2 as the receptor for binding and entry13,21, which we further confirmed by flow cytometry analysis and competitive inhibition experiment using soluble hACE2 in this study (Fig. 3b, c). While full-length S proteins of SARS-CoV-2 and SARS-CoV S share almost 76% identities in amino acid sequences, the NTDs show only 53.5% of homology. Of note, NTDs of different CoVs S proteins have been shown to bind different sugar. While NTD of MERS-CoV prefers α2,3-linked sialic acid over α2,6-linked sialic acid47, NTDs of human CoVs OC43 and HKU1 bind to 9-O-acetylated sialic acids48,49. No sugar binding has been reported for NTD of SARS-CoV. Whether or not NTD of SARS-CoV-2 binds to sugar and whether sugar binding of NTD affects virus entry remains to be determined.