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We developed a quantitative single-particle imaging assay that classifies fluorescent virus-like particles (VLPs) as surface, crossing, or internal on HEK293T-ACE2 cells, separating binding from internalization. Comparing G614 and Omicron BA.5 S protein variants, G614 showed higher binding and a larger internalized fraction at baseline. A trivalent anti-S protein aptamer reduced G614 binding and internalization but increased BA.5 internalization. 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