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Stanford Bio-X Seminar: David Veesler - "Structural studies of coronavirus fusion glycoproteins"

June 03, 2020 1:00 PM to 2:00 PM
This seminar will be held over Zoom
Event Type: 

Stanford Bio-X Seminar – Structural studies of coronavirus fusion glycoproteins

David Veesler, Assistant Professor of Biochemistry, University of Washington


Hosted by: Dr. Georgios Skiniotis, Professor of Molecular & Cellular Physiology, Structural Biology, and Photon Science, Stanford University

Coronavirus spike (S) glycoprotein trimers promote entry into cells and are the main targets of the humoral immune response. We demonstrated that ACE2 is a functional entry receptor for this novel coronavirus and that the receptor-binding domains of SARS-CoV-2 S and SARS-CoV S bind with similar affinities to ACE2, which correlates with the efficient spread of SARS-CoV-2 among humans. We determined cryo-electron microscopy structures of the SARS-CoV-2 S ectodomain trimer, demonstrating spontaneous opening of the receptor-binding domain, and providing a blueprint for the design of vaccines and inhibitors of viral entry. SARS-CoV S murine polyclonal sera potently inhibited SARS-CoV-2 S-mediated entry into target cells, indicating that cross-neutralizing antibodies targeting conserved S epitopes can be elicited upon vaccination. We subsequently isolated a monoclonal antibody from the memory B cells of an individual who was infected with SARS-CoV in 2003 and show that it potently neutralizes SARS-CoV-2 and SARS-CoV pseudoviruses as well as authentic SARS-CoV-2 . Our results pave the way for using S309- and S309-containing antibody cocktails for prophylaxis in individuals at high risk of exposure or as a post-exposure therapy to limit or treat severe disease.

June 3rd, 2020 at 1:00 PM over Zoom
 

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