Glycan Hopscotch: coronavirus’ dynamic journey from animals to humans

Coronaviruses (CoV), diverse viruses of high zoonotic potential, take advantage of carbohydrates for initial recruitment at the host cell surface.

Such interactions are highly dynamic and need to be tightly regulated to ensure virus diffusion through glycan-rich physical barriers in the respiratory tract, the mucus and the glycocalyx, followed by efficient transfer to an entry receptor for optimal infection.We hypothesize that successful zoonotic transmission requires optimal virus- carbohydrate interaction in the target tissue.

We further speculate that the fine-tuning of the dynamic interaction with the cell surface is an important contribution in the evolution of the virus in the human population towards becoming endemic, with milder symptoms but higher transmissibility in the case of severe acute respiratory syndrome CoV-2 (SARS-CoV-2).To challenge these hypotheses, we systematically investigate how SARS-CoV-2, and closely related bat coronaviruses, are adapting to interact with the human glycome, by evolving the dynamics of heparan sulfate-mediated virus interactions at the cell surface.

This will be achieved by capitalizing on my lab’s unique biophysical assay toolbox to study how the viruses attach, detach, diffuse, and penetrate the surface of a host cell.A better understanding of the mechanisms leading to CoV infection and of the factors determining zoonotic spillover, virulence and transmissibility will make us better prepared to fight future emerging diseases.