Sialic acids are commonly found in cellular secretions and on external surfaces of cells as terminal motifs attached to glycoproteins and glycolipids (i.e., gangliosides) (Schauer, 2009). Sialyation was reported to mediate the binding and spreading of many viruses. Sialyation exhibits dual properties with respect to intercellular communication, either mediating viral binding and recognition, or acting as a “mask” in suppressing immunoreactivity by shielding cellular antigenic sites (Nimmerjahn et al., 2007). The precise effect of sialyation is dependent on specific substituents attached to the sialic acid moiety (Schauer, 2009). In addition to deploying specific lipids in their binding to host cells, viruses may also hijack the host’s endogenous machinery to achieve intercellular spreading. For example, hitherto evidence was present that implicated multivesicular bodies (MVBs)/late endosomes in the extracellular release of hepatitis C virus (HCV) and human immunodeficiency virus (HIV) (Chapuy-Regaud et al., 2013). Retrograde movement of MVBs and subsequent fusion with the plasma membrane release entrapped viral particles into the circulation to infect distant cells. Intracellular accumulation of HIV particles that have escaped lysosomal degradation near the plasma membrane periphery attracts and infects surveying CD4+ T cells via formation of infectious synapse (i.e., trans-infection) (Yu et al., 2014). Coronaviruses, on the other hand, were shown to usurp the trafficking machinery of endoplasmic reticulum-Golgi intermediate compartment (ERGIC), and mature viral particles are released by infected cells in the form of transport vesicles budding from the trans-Golgi network (TGN) (Hong, 2020). In this aspect, the coronavirus murine hepatitis virus strain A59 (MHV-59) was found to exploit the TGN to reach the cell exterior (Tooze et al., 1987), while the Middle East respiratory syndrome (MERS) virus was shown to contain a TGN-localization signal in the C-terminal domain of its M protein (Perrier et al., 2019). Biosynthesis of gangliosides in mammals takes place via stepwise addition of monosaccharides and sialic acid motifs to ceramides at membranes of the Golgi and TGN (Sandhoff and Sandhoff, 2018). Trafficking routes connecting the Golgi apparatus and late endosomes are present (Gruenberg and Stenmark, 2004). For example, the mannonse-6-phosphate receptor (MPR) cycles between the late endosomes and TGN (Gruenberg and Stenmark, 2004; Kobayashi et al., 1998). Disrupting the homeostasis of bis(monoacylglycero)phosphate (BMP), a unique lipid localized to the MVBs, led to mis-sorting of MPR and their accumulation in late endosomes (Kobayashi et al., 1998).