(A) Knockdown of LDLR expression by siRNA impairs S protein pseudovirion infection of ARPE-19 cells. ARPE-19 cells were transfected with siRNAs for LDLR, GAPDH, scrambled (1 and 2), and LDLR-scrambled and infected with SARS-CoV-2 spike pseudotyped virus at MOI 10 for 24 h. Microscopy images were taken at 72 h post-infection. The graph shows the fold difference in the uptake of original spike-pseudotyped lentiviruses in the presence of various siRNAs (25 pmol; Supplementary Table S1), compared to untreated controls infected with original spike protein pseudotyped particles alone. * p < 0.01, ** p < 0.001, *** p < 0.0005, **** p < 0.0001 in unpaired with unequal variances student’s t-test. (B) Regression analysis for LDLR protein amount in ARPE-19 samples and uptake of S-protein pseudotyped lentiviruses by ARPE-19 cells.