Therapeutic Targeting of Viral N-Glycosylation Modification: From Molecular Mechanisms to Clinical Application Prospects.

Viral diseases represent a significant global health challenge. N-glycosylation, a critical post-translational modification, plays diverse and essential roles throughout the viral life cycle. This review outlines the initiation of N-glycosylation, elucidating its role in facilitating viral protein synthesis within the endoplasmic reticulum (ER). This process ensures proper protein folding and functionality through stringent quality control mechanisms. Consequently, targeting N-glycosylation offers substantial potential for developing antiviral therapies. Specific antiviral strategies include inhibiting glycosyltransferase activity to block the initial glycosylation step and employing glucosidase inhibitors to disrupt viral protein glycosylation, leading to envelope protein misfolding. Additionally, this review explores other mechanisms of glucosidase inhibitors, including their dual role in modulating the ER-associated degradation (ERAD) pathway. The clinical evaluation of investigational antiviral agents is also addressed, providing a comprehensive analysis of their efficacy in suppressing viral replication and associated adverse effects. To advance precise antiviral interventions, future research must deepen the understanding of these mechanisms while optimizing the balance between efficacy and long-term safety in drug design. Such efforts are crucial for translating laboratory findings into effective clinical applications.