Glycans are ubiquitously expressed sugars, coating the cell and protein surfaces. They are found on many proteins as either short and branched chains or long chains sticking out from special membrane proteins, known as proteoglycans. This sugar cushion, the glycocalyx, modulates specific interactions and protects the cell. Here it is shown that both the expression of proteoglycans and the glycans expressed on the surface of both the host and virus proteins have a critical role in modulating viral attachment to the cell. A mathematical model using SARS-Cov-2 as an archetypical virus to study the glycan role during infection is proposed. It is shown that this occurs via a tug-of-war of forces. On one side, the multivalent molecular recognition that viral proteins have toward specific host glycans and receptors. On the other side, the glycan steric repulsion that a virus must overcome to approach such specific receptors. By balancing both interactions, viral tropism can be predicted. In other words, the authors can map out the cells susceptible to virus infection in terms of receptors and proteoglycans compositions.

Molecular Dynamics (MD) is a method used to calculate the movement of atoms and molecules broadly applied to several aspects of science. It involves computational simulation, which makes it, at first glance, not easily accessible. The rise of several automated tools to perform molecular simulations has allowed researchers to navigate through the various steps of MD. This enables to elucidate structural properties of proteins that could not be analyzed otherwise, such as the impact of glycosylation. Glycosylation dictates the physicochemical and biological properties of a protein modulating its solubility, stability, resistance to proteolysis, interaction partners, enzymatic activity, binding and recognition. Given the high conformational and compositional diversity of the glycan chains, assessing their influence on the protein structure is challenging using conventional analytical techniques. In this manuscript, we present a step-by-step workflow to build and perform MD analysis of glycoproteins focusing on the SPIKE glycoprotein of SARS-CoV-2 to appraise the impact of glycans in structure stabilization and antibody occlusion.

The general perception of viruses is that they are small in terms of size and genome, and that they hijack the host machinery to glycosylate their capsid. Giant viruses subvert all these concepts: their particles are not small, and their genome is more complex than that of some bacteria. Regarding glycosylation, this concept has been already challenged by the finding that Chloroviruses have an autonomous glycosylation machinery that produces oligosaccharides similar in size to those of small viruses (6-12 units), albeit different in structure compared to the viral counterparts. We report herein that Mimivirus possesses a glycocalyx made of two different polysaccharides, now challenging the concept that all viruses coat their capsids with oligosaccharides of discrete size. This discovery contradicts the paradigm that such macromolecules are absent in viruses, blurring the boundaries between giant viruses and the cellular world and opening new avenues in the field of viral glycobiology.