P681R appears better than P681H in Delta, and the other way around in Alpha.


That could be a false signal from a founder effect, but after this much time and selective pressure, I seriously doubt it.  It's the other residues for Delta and Alpha that are most interesting, because P681H alone in Alpha does little and Delta stinks with H681 or P681.


This paper reports that Alpha with H681(GISAID accession EPI_ISL_999340) is more infectious than Delta with P681.  Delta with R681 obviously dominated.  Alpha's RBD has 200x the binding affinity for hACE2 as compared to Delta's RBD.

Unfortunately, they did not test Alpha with H681R.  It is likely that another one of Delta's mutations is required to make P681R so synergistic, so I no examination of that or synergistic mutations for P681H in Alpha to be a serious omission from this work, and I've served on enough review panels to say that.

Anyway, I think this is the main takeaway: antigenic drift is wider than presumed, and haplotypes linger.  Perhaps waiting for the immune response specific to them to wear off, some strains are more in transmission bottlenecks than they are en route to extinction, in this case Alpha due to Delta's superiority today.  Alpha and Delta are not far enough apart antigenically for Alpha to recover yet, and it may still die out, but it should drift far enough eventually.

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