Establishment of SARS-CoV-2 Cell Models

A549-hACE2 [a gift from Dr. Ben tenOever^{3 (link)}], 293 T, HEK293, A549, and 3T3-L1 pre-adipocyte cell lines (refer to Supplementary Table 1) were cultured in DMEM and 10% FBS. U937, Calu-3, and HCT116 cells were cultured in RPMI, EMEM, and McCoy’s 5 A media, respectively, with 10% FBS. Caco-2 cells were cultured in EMEM with 20% FBS. Vero E6-TMPRSS2 cells were generated by lentiviral transduction of Vero E6 (CRL-1586) cells and were maintained in DMEM containing 10% FBS and 20 μg/mL blasticidin (Invivogen). All media were supplemented with glutamine and penicillin–streptomycin. EPRS1 knockdown in 3T3-L1 pre-adipocytes was generated by CRISPR, and adipocytic cell differentiation was done using Adipogenesis Assay Kit (Cayman Chemicals) per manufacturer’s protocol^{54 (link)}. HEK293‒3′-end, SPEAR, and GU-mutant cell lines were made by reporter plasmid transfection and G418 (800–1000 ng/ml) selection over five passages. A549-hACE2‒3′-end/SPEAR element and Caco-2‒3′-end/SPEAR element cell lines were made similarly with selection at 600 and 800 ng/ml of G418, respectively.