“…Given previous results using indirect detergent fractionation readouts (McBride and Machamer, 2010b;Petit et al, 2007), we were surprised to observe that SARS-CoV-2 spike does not partition strongly into GPMVs' dense, ordered phase (L o ) (Figure 6D), which is enriched for cholesterol and sphingolipids (Levental et al, 2009;. Moreover, in our cell fusion assay, treatment with the raft-disrupting drug myriocin, which depletes sphingolipids from the plasma membrane (Castello-Serrano et al, 2020), did not inhibit fusion (Figure 6F,G). Thus, SARS-CoV-2 spike protein appears to facilitate membrane-fusion in a manner that is dependent on palmitoylation of its uniquely cysteine-rich CTD, but through a mechanism unique from canonical membrane nanodomains, although we cannot rule out a discrepancy in lipid raft properties between GPMVs and living cells (Levental et al, 2020).…”