Viral protein glycosylation

Viral protein glycosylation is a critical post-translational modification where host-cell enzymes are utilized to attach and process glycans on viral proteins, particularly surface envelope glycoproteins [13, 14]. This modification occurs within the endoplasmic reticulum (ER) and Golgi apparatus and is vital for the correct folding and structural stability of viral proteins, as well as the assembly and budding of progeny virions [3, 9]. Beyond structural roles, the 'glycan shield' formed by these sugars masks immunogenic protein epitopes from the host's immune system, facilitating immune evasion and persistent infection [7, 12]. Additionally, specific glycans mediate viral attachment and entry into host cells by interacting with cellular receptors and lectins like DC-SIGN [10, 14]. Therapeutic interventions often involve iminosugars that inhibit host ER alpha-glucosidases, leading to the accumulation of misfolded viral proteins that are degraded before they can be incorporated into infectious particles [1, 5]. This approach provides a broad-spectrum antiviral strategy applicable to diverse enveloped viruses, including HIV, Hepatitis B, Influenza, and SARS-CoV-2 [4, 6].

Other names

Viral N-glycosylationViral glycan shield formationViral glycoprotein processingN-linked glycosylation of viral proteinsViral O-glycosylation

Drugs targeting this process primarily inhibit host-cell endoplasmic reticulum (ER) alpha-glucosidases I and II. These enzymes are responsible for the sequential trimming of terminal glucose residues from nascent N-linked glycans, a step required for the glycoprotein to interact with ER chaperones like calnexin and calreticulin. Inhibition leads to the production of misfolded viral glycoproteins that are subsequently degraded via the ER-associated degradation (ERAD) pathway, preventing the assembly of infectious virions [1, 4, 5]. Alternatively, carbohydrate-binding agents (CBAs) such as lectins bind directly to intact viral glycans, blocking viral entry and potentially forcing the virus to delete portions of its glycan shield, which exposes it to immune neutralization [7].