Speaker: David Veesler, Assistant Professor - Department of Biochemistry, University of Washington

Title: Structural Studies of Coronavirus Fusion Proteins

Abstract: Recent outbreaks of severe acute respiratory syndrome and Middle-East respiratory syndrome along with the threat of a future coronavirus-mediated pandemic underscore the importance of finding ways to combat these viruses. The trimeric spike transmembrane glycoprotein promotes entry into host cells and is the major target of neutralizing antibodies upon infection. To understand the adaptive immune response elicited upon natural infections with coronaviruses, we used cryo-electron microscopy to characterize the SARS-CoV and MERS-CoV spike glycoproteins in complex with monoclonal neutralizing antibodies isolated from human survivors. Although the two antibodies studied blocked attachment to the respective host cell receptor, only the anti-SARS-CoV S antibody triggered fusogenic conformational changes via receptor functional mimicry. These results provide a structural framework for understanding coronavirus neutralization by human antibodies and shed light on activation of coronavirus membrane fusion, which takes place through a receptor-driven ratcheting mechanism.