Jesse Bloom PRO
Scientist studying evolution of proteins and viruses.
Fred Hutch Cancer Research Center / HHMI
Slides at https://slides.com/jbloom/anticipatory-sars-cov-2
Phylogenetic tree of 434,167 full-length SARS-CoV-2 genomes provided by GISAID
Impossible to measure true viral fitness in the lab, so we focus on biochemical phenotypes that contribute to fitness. For RBD:
1) Does RBD fold properly?
2) Does RBD bind ACE2 with high affinity?
3) Is RBD bound by anti-viral antibodies?
Impossible to measure true viral fitness in the lab, so we focus on biochemical phenotypes that contribute to fitness. For RBD:
1) Does RBD fold properly?
2) Does RBD bind ACE2 with high affinity?
3) Is RBD bound by anti-viral antibodies?
Evolutionary pressure is to maintain these two phenotypes...
... while changing this phenotype.
RBD
fluorescent ACE2
yeast
fluorescent tag on RBD
Maps for four individuals; for more see
501Y.V2 also known as B.1.351, originally identified in South Africa.
501Y.V3 also known as P1, originally identified in Brazil.
Complete mutational scanning of biochemical phenotypes
Pseudotype virus escape selections and neutralization assays
Live virus escape selections and neutralization assays
Increasing "authenticity"
Increasing throughput
E484K was first observed in sequenced isolates in March of 2020 (three times!). If we'd had a good phenotypic lookup table, that would have been plenty of time to move up the hierarchy of experimental authenticity and start preparing.
By Jesse Bloom
Anticipatory evolution of SARS-CoV-2
Scientist studying evolution of proteins and viruses.