Investigating the carbohydrate binding fine-specificity of the human betacoronaviruses, HCoV-OC43 and HCoV-HKU1.

Coronaviruses are a family of viruses that cause disease in mammals and birds and can be categorized into two groups - those that use proteins as receptors and those that use sugars (carbohydrates) as receptors. For protein binding coronaviruses, we have a good understanding of how they interact with their receptors, and how they enter our cells. For carbohydrate binding coronaviruses however, we have a very limited understanding of the receptors they use beyond a requirement for sialic acid, a type of sugar commonly found on cell surfaces. Our previous work has shown that various strains of carbohydrate binding coronaviruses have differences in their sugar binding site, with some strains containing bulky insertions. As a result of these bulky inserts, coronaviruses do not bind to all sialic acid-containing carbohydrates in the same way, with some viruses binding weaker than others. Our hypothesis is that the differences found in the various strains dictate the carbohydrate binding specificity of these viruses. We think that strains that have bulky insertions are restricted from binding short carbohydrates and can only bind long carbohydrates, and that strains that do not contain the insertions are able to bind to both short and long carbohydrate receptors. We plan to test our hypothesis by producing short and long carbohydrates, and testing their binding to the various coronavirus strains. Additionally, we will solve the atomic structures of the carbohydrate-coronavirus complexes to determine how exactly the bulky insertions affect carbohydrate receptor binding. Our work will shed light on the receptor interactions for a disease causing group of viruses with pandemic potential that are relatively understudied, and will hopefully lay the groundwork for future vaccine and therapeutic development.