Thread by @iamgkadam

While this is indeed a hugely mutated form of #SARSCoV2 when compared to the "original" sequence from the Wuhan patient, its a bit exaggerated to say this as evidence of any evolutionary rate. Tanazania, and all Africa's, level of infections is likely far underdetected after all

https://twitter.com/K_G_Andersen/status/1375292808278372358

With little understanding of the level of underdetection, could be easily be a couple immunocompromised hosts + few transmissions. Or The 18907 V->F is in nsp14 and might impact Rdrp proofreading. All said, any claims on immune evasion/transmissibility are only hypotheses now

However, such data also shows the power of genomic sequence surveillance as much as possible to both understand the underlying biology and prepare for potential public health ramifications.

Its also easily misused for fear mongering - one thing to stay guarded against.

Oooh. V->F (green) is indeed very close to the SAH-GpppA substrate (dark blue). Might well impact how good nsp14 is at proofreading? Maybe F packs better against the aromatic rings of the substrate? PDB 5C8S
Did best I could w RCSB viewer, no pymol 😭
@klausenhauser @nmrkaygee

@babarlelephant
Has the unthinkable happened w nsp14 mutating now? This has been documented once before in nextstrain it seems, although I think this is only a subsample.

https://twitter.com/iamgkadam/status/1356588506454380546?s=20

@klausenhauser @nmrkaygee @wanderer_jasnah did point out something I had missed about this "active site" - it is indeed one, but not the one in the exonuclease domain. The two domains might still communicate in ways beyond what we know so far (which is they don't seem to)

https://twitter.com/iamgkadam/status/1375619510305165315?s=20