The spike proteins of SARS-CoV-2 and the closely related bat coronavirus RaTG13 differ in their binding affinity of human ACE2. This is due to differences in the receptor binding domain (RBD), the region primarily responsible for ACE2 binding, which are only 89% identical on the amino acid level, compared to 96% for the remainder of their genomes.
ORIGINAL PAPER
Combinatorial mosaics dissect the residue level basis of ACE2 binding divergence between SARS-CoV-2 and RaTG13
WHAT WE KNOW
Here, we constructed a combinatorial library of RBD mosaics containing combinations of 18 amino acid differences between SARS-CoV-2 and RaTG13 and measured human ACE2 binding using yeast surface display and fluorescence-activated cell sorting. The mosaics revealed a broad range of binding phenotypes. The effects on ACE2 binding were concentrated at eight positions, including all six variable positions that directly contact ACE2.
WATCH NEXT
Review the primary source, validate the main result, and establish whether any listed-company transmission is direct.
EVIDENCE
What the evidence supports so far
Research signals
Classification pending.
What remains unverified
The full methodology, effect size, and limitations still require analyst review.
Company impact remains unverified until a direct economic transmission is established.