A549 are a cell line that do not express ACE2 receptors. Partridge et al. observed that SARS-CoV-2 S protein interact with these cells even though they do not express ACE2. Further studies were conducted using two types of 293T cells: cells that express low amounts of ACE2 and cells that over-express ACE2. S protein interacted with both cell types, but the binding affinity for those expressing low amounts of ACE2 was nearly undetectable. This suggests that the S protein, specifically the S1 and S2 subunits, may initially interact with host cells via a different receptor. However, binding affinity studies suggest that the viral receptor binding domain (RBD) requires higher expression levels of ACE2 to interact with cells.