N-glycoproteomic Profiling Revealing New Coronavirus Therapeutic Targets That Maybe Involved in Cepharanthine’s Intervention

Abstract

N-glycosylation is an important post-translational modification involved in protein folding, signal transduction, extracellular matrix organization and immune response. Evidence showed that glycosylated SARS-CoV-2 Spike protein may be a potential target in viral pathogenesis and drug/vaccine design. To investigate the mechanism of coronavirus infestation and drug targets from glycosylation perspective, we constructed a SARS-CoV-2 cellular model using GX_P2V-infected VeroE6 cells to study the effects of GX_P2V on glycoproteins in presence or absence of Cepharanthine (CEP) through N-glycoproteomics profiling. The results showed that coronavirus GX_P2V could cause aberrant protein glycosylation, whereas CEP can partially maintain GX_P2V-induced aberrant glycoproteins at homeostasis. Further study revealed that proteins LAMB1 and FN1 were pivotal in counteracting coronavirus-induced aberrant protein glycosylation by CEP. Furthermore, CEP can dramatically regulate the glycosylation of viral proteins S, M and N. Our results suggest that despite the strong anti-coronavirus effects of CEP, drug combinations need be considered to achieve optimal therapeutic strategies.