Fig. 5. SARS-CoV-2 S leakage to the plasma membrane facilitates cell-cell fusion and the formation of syncytia.

a Comparison of the cytoplasmic tails of S proteins from the four genera of Coronaviridae, aligned by their TMDs. Binding motifs for trafficking proteins are indicated, along with cysteine residues (orange). b Representative micrographs showing 293T cells coexpressing mCherry and different full-length S variants fusing with acceptor Vero cells stained with CellTracker Green. Cell fusion is monitored by overlap between the green and red signal. Retention of S in the ER reduces its capacity to form syncytia while increased leakage to the plasma membrane increases it. Scale bars: 200 µm. c Quantification of cell-cell fusion as percentage of the field showing green and red overlap. Mean of two biological replicates (see Source Data file). d Immunoblots from 293T cells expressing the indicated full-length S variants, with the H1271K mutation preventing the protein from reaching the site of S1/S2 cleavage by furin in the late Golgi. Representative of two independent replicates.