Université Laval

Purpose

SARS-CoV-2 spike protein plays a critical role in initiating the infection process. There is evidence that in addition to the recognition of its receptor binding domain (RBD) by human ACE2 receptor, interactions of the N-terminal domain (NTD) with the sialic acid-based glycan receptors lining the respiratory tract are important to trigger its binding to ACE2, but structural determinants of this recognition remain elusive. As the atomic details of these interactions could be exploited to design and optimize therapeutic candidates, the Recipient will determine a series of crystal structures of spike domains complexed with various ACE2-derived peptides and glycan carbohydrates. Structural data generated will provide a solid basis for further engineering of both peptides and glycans with incremental improvements of binding and neutralization properties to the SARS-CoV-2 spike protein, paving the way for development of therapeutic candidates that can address not only the current pandemic but also future challenges.