Functional role of the glycan shield in the activation of the SARS-CoV-2 S protein

Elisa Fadda / Maynooth University, Ireland

June 10, 2021, 3 - 4 pm (CEST)

Online live talk


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 [1].

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 [2] and how specific glycoforms and changes in the shield’s topology due to viral evolution may modulate its binding to ACE2 [3]. 

[1] Watanabe, Y., Allen, J. D., Wrapp, D., McLellan, J. S., Crispin, M., Science (2020).

[2] Casalino, L., Gaieb, Z., Goldsmith J., Hjorth C., Dommer, A., Harbison, A., Fogarty, C.,
      Barros, E., Taylor, B., McLellan J., Fadda, E., Amaro, R., ACS Central Sci (2020).

[3] Harbison, A., Fogarty, C., Phung, T., Satheesan, A., Schulz, B., Fadda E., bioRxiv (2021)

Elisa Fadda

Elisa Fadda received her BSc and MSc in Chemistry from the Università degli Studi di Cagliari in 1999. Then, she moved to the Université de Montreál where under the supervision of Professor Dennis R. Salahub she worked on the development of ab initio QM methods for the prediction of NMR shieldings from time-dependent density-functional theory (TD-DFT). For this work she was awarded her PhD in 2004. From 2004 to 2008, Elisa did her post-doctoral studies at the Hospital for Sick Children Research Institute in Toronto on large scale simulations based on classical mechanics of ions translocation in respiratory chain proteins and ion channels. Then, she moved to Professor Robert J. Woods' Computational Glycoscience laboratory at the National University of Ireland in Galway where she studied the simulation of glycoproteins and glycan-processing enzymes. From 2013 to 2014, she held a position as assistant lecturer in the Department of Chemistry at Maynooth University in Ireland. She stayed there and since 2014, Elisa is an assistant professor and PI of the Computational Glycoscience research group.