Impact of Glycosylation on the Structural Dynamics of the Dengue Virus Serotype 2 Envelope Protein

Glycosylation plays a crucial role in modulating the structural and functional properties of viral envelope proteins. In this study, we investigated the influence of N-linked glycosylation on the conformational dynamics of the envelope (E) protein of dengue virus serotype 2 (DENV-2), a key factor in viral entry and immune recognition. Dengue is a mosquito-borne viral disease transmitted by Aedes mosquitoes, affecting millions annually in tropical and subtropical regions. It ranges in severity from mild fever to severe forms such as dengue hemorrhagic fever and dengue shock syndrome. Dengue virus has four serotypes (DENV-1 to DENV-4), and the E protein is essential for mediating viral entry into host cells, by facilitating receptor binding and membrane fusion. Using molecular dynamics simulations and comparative structural analysis, we evaluated the behavior of the glycosylated forms of the E protein. Based on the literature, we hypothesized that glycosylation at specific asparagine residues modulates the flexibility and interdomain movements of regions involved in receptor binding and membrane fusion. Our results suggest that glycans impact solvent accessibility and local secondary structures stability, potentially influencing epitope shielding and immune recognition. These findings support the idea that glycosylation is not merely a structural feature but a potential active modulator of viral protein function. Understanding these effects provides insights into the mechanisms of viral infectivity and immune evasion mechanisms and may guide the development of vaccines or antiviral therapies targeting glycan-dependent conformational states. This work highlights the importance of post-translational modifications in the dynamic behavior of viral surface proteins. 

This work was supported by Capes, CNPq (409272/2021-3) and FAPESP (2022/00347-0 and 2022/07231-7)