Jesse Bloom - August 26, 2020

Jesse Bloom, PhD, Associate Professor, Fred Hutch Cancer Research Center, Affiliate Associate Professor, Genome Sciences & Microbiology, University of Washington, Investigator, Howard Hughes Medical Institute, "The evolutionary potential of the SARS-CoV-2 Spike" The presentation introduced the mechanism of receptor-binding domain (RBD).

With the use of deep mutational scanning to map functional constraints on SARS-CoV-2 RBD, the research group was able to identify the structure-function relationship, analyze SARS-CoV-2 genetic variation, and understand the functional diversity in scarbecovirus RBDs. DMS measurement has been applied to assess the affinity and stability of the RBDs. In general, research shows that mutations that increase ACE2 binding enhance infectivity by spike-pseudotyped lentivirus. Also, there are single mutations that dramatically improve RBD expression and stability, which might be helpful for vaccines. RBD variation is shaped by purifying selection. To summarize, the research group can map the effects of all mutations on ACE 2binding and RBD expression. It is useful for understanding viral evolution and is interesting to apply more broadly to scarbecoviruses and ACE2 homologs. The research group can completely map antibody escape mutations. Also, it is useful for designing antibody cocktails and understanding the antigenic consequences of mutations.