Thread by @jbloom_lab

For anyone who doesn't want to do alignments, here are spike amino-acid mutations separating #SARSCoV2 from newly discovered bat CoV BANAL-20-52, which is #SARSCoV2's closest known relative in spike.

Mutations as #SARSCoV2 Wuhan-Hu-1 to BANAL-20-52 in #SARSCoV2 numbering. (1/6)

There are 16 amino-acid substitutions across the 1273-residue spike.

In addition, there is an indel at the furin cleavage site, since like all other known bat sarbecoviruses, BANAL-20-52 lacks the furin cleavage site found in #SARSCoV2. (2/6)

For comparison, Beta and Delta #SARSCoV2 variants each have 7 amino-acid substitutions relative to Wuhan-Hu-1.

So BANAL-20-52 spike about twice as diverged as current #SARSCoV2 variants are from early #SARSCoV2, *plus* of course BANAL-20-52 lacks the furin cleavage site (3/6)

5 amino-acid mutations separate the RBDs of early #SARSCoV2 and BANAL-20-52 (R346T, A372T, I402V, Q498H, & H519N).

From our deep mutational scanning (jbloomlab.github.io/SARS-CoV-2-RBD…), we expect Q498H to make BANAL-20-52 RBD have *stronger* affinity for human ACE2 than #SARSCoV2. (4/6)

From our deep mutational scanning (jbloomlab.github.io/SARS2_RBD_Ab_e…), we expect two of the RBD mutations (R346T & Q498H) to impact binding of some antibodies targeting RBD, with overall antigenic difference likely to be on par w antigenic change in current #SARSCoV2 variants. (5/6)

For reference, BANAL-20-52 described in this pre-print: researchsquare.com/article/rs-871… (6/6)

And to clarify, above should say Beta and Delta each have 7 *spike* amino-acid substitutions relative to Wuhan-Hu-1. Hopefully clear from context of thread that this refers only to spike.