Protein glycosylation plays a crucial role in viral pathogenesis, as suggested by the extensive N-glycosylation coat on viral fusion proteins. Recent structural and glycoanalytic studies have shown that the SARS-CoV2 spike (S) protein is not shielded as effectively as the envelope glycoproteins of “evasion strong” viruses, with the receptor binding domain (RBD) exposed to potential antibody recognition. Also, experimental evidence indicates important differences in the type of glycosylation, where complex, rather than oligomannose N-glycans, constitute the majority of the SARS-CoV2 S shield .
Understanding the specific functions of this unique glycosylation pattern is particularly tricky because of the glycans' intrinsic conformational disorder prevents them from being easily characterised with standard structural biology techniques. In this talk I will present how high-performance computing (HPC) molecular simulations have contributed to advance our knowledge on the role of glycosylation in the SARS-CoV2 infection mechanisms. I will focus in particular on how we identified a unique functional role of the glycan shield in the activation of the S glycoprotein  and how specific glycoforms and changes in the shield’s topology due to viral evolution may modulate its binding to ACE2 .
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