Fig. 10.

Schematic of the 2-DG-mediated impairment of viral GP-C N-glycosylation and cleavage. LCMV glycoprotein is synthesized as a single glycoprotein precursor complex (GP-C) with N-terminal stable signal peptide (SSP) that targets the protein to the endoplasmic reticulum (ER) and is subsequently co-translationally cleaved. Post-translationally, GP-C undergoes extensive N-glycosylation and cleavage into GP1 and GP2, which occurs in the Golgi apparatus (GA) or post-Golgi compartment. The mature tripartite complex SSP/GP1/GP2 forms a functional spike glycoprotein of LCMV. 2-deoxy-D-glucose (2-DG) competes with mannose for incorporation into lipid-linked oligosaccharide precursors that are assembled at the membrane of the ER and further used for protein N-glycosylation. As a result, in the presence of 2-DG, synthesized GP-C is not glycosylated, which has a negative impact on its cleavage into GP1/GP2 and the formation of functional spike glycoproteins. Created with BioRender.com