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Stanford Bio-X Seminar 'Structural Studies of Coronavirus Fusion Glycoproteins': Dr. David Veesler, University of Washington

June 3, 2020 - 1:00pm to 2:00pm

Research Seminar

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

Abstract: 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.


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Event Sponsor: 
Stanford Bio-X