Beyond Shielding: The Roles of Glycans in the SARS-CoV-2 Spike Protein

-glycans at sites N165 and N234 in modulating the conformational dynamics of the spike's receptor binding domain (RBD), which is responsible for ACE2 recognition. This finding is corroborated by biolayer interferometry experiments, which show that deletion of these glycans through N165A and N234A mutations significantly reduces binding to ACE2 as a result of the RBD conformational shift toward the "down" state. Additionally, end-to-end accessibility analyses outline a complete overview of the vulnerabilities of the glycan shield of the SARS-CoV-2 S protein, which may be exploited in the therapeutic efforts targeting this molecular machine. Overall, this work presents hitherto unseen functional and structural…

• NS
  National Science Foundation

  Awards: 1818253, MCB-2032054, OAC-1818253, 2032054
• RC
  Research Corporation for Science Advancement
• SU
  State University of New York
• MS
  Michigan State University
• UO
  University of Southampton
• UO
  University of Bristol
• IR
  Irish Research Council
• IC
  Irish Centre for High-End Computing
• SU
  Sorbonne Université
• NI
  National Institutes of Health

  Awards: GM132826, AI127521, R01-AI127521
• CO
  College of Engineering, Michigan State University
• UO
  University of California, San Diego
• NI
  National Institute of General Medical Sciences

  Award: GM132826
• NI
  National Institute of Allergy and Infectious Diseases

  Award: R01-AI127521
• DO
  Division of Molecular and Cellular Biosciences

  Award: RAPID MCB-2032054