Thread by @TimothyChase

@lalani_safina @giorgilab (1/n) Actually the T478K mutation is found in "Delta" B.1.617.2. as you can tell was the substitution from T to k we are looking at a neutrally charged amino acid being replaced by a positively charged amino acid which means that it will be more difficult...

@lalani_safina @giorgilab (2/n) for the immune system to create antibodies that will counteract it. However at least with the variant discovered in Mexico we found that this mutation has an especially high free binding energy to the ACE2 receptor. As such it binds much more tightly to the receptor and...

@lalani_safina @giorgilab (3/n) this likely explains much of the increased transmissibility.

Regarding Delta:

"In particular, the Spike protein contained 9
mutations, when compared to the D614G strain (belonging to the basal B.1 lineage) used here as a
reference, including five mutations..."

@lalani_safina @giorgilab (4/n) "in the NTD. (T19R, G142D, Δ156, Δ157, R158G), two in the RBD
(L452R, T478K), one mutation close to the furin cleavage site (P681R) and one in the S2 region (D950N)..."

biorxiv.org/content/10.110…

@lalani_safina @giorgilab (5/n) L452R is likewise in the binding interface and it has been suggested that it is responsible for much of the increased expansion of the variants that harbor it.

Please see:

biorxiv.org/content/10.110…

@lalani_safina @giorgilab (6/n) L452R alsoi appears to diminish cellular immunity.

Please see:

rapidreviewscovid19.mitpress.mit.edu/pub/jcavas70/r…

@lalani_safina @giorgilab (7/n) Anyway, I focus on a few of the "Delta" B.1.617.2 mutations here:

https://twitter.com/TimothyChase/status/1397215145982529537?s=19

... getting into escape from cellular immunity, for example, but there is a great deal more I would like to explore, e.g., enhanced syncytia formation due to L452R and P681R,...

@lalani_safina @giorgilab (8/8) particularly in the lungs and it's effects on t-cell immunity, but that will have to wait until I have more time.