Thread by @TRyanGregory

When a new variant is designated with a PANGO label, its distinguishing mutations are listed. So, for example, you may see that "EG.5 = XBB.1.9.2 + S:F456L + ORF1a:A690V + ORF1a:A3143V", and "EG.5.1 = EG.5 + S:Q52H". But what does that notation mean? 🧵

The SARS-CoV-2 genome contains a number of protein-coding regions (genes), the one we hear about most being the spike protein (S). There are also "open reading frames" (ORFs), which are regions in between a start and stop codon -- that is, a sequence that can be read as a gene.

The letters before the colon in the mutation notation refer to the gene or open reading frame that has undergone a mutation. In the example from EG.5 and EG.5.1, that's "S" (spike) and "ORF1a" (open reading frame 1a).

The first letter after the colon is the amino acid that was present at that position in the original protein, the number is the position of the changed amino acid in the protein sequence, and the last letter is the new amino acid that is now specified in the mutated sequence.

Here is a list of the amino acids and their abbreviations.

So, S:F456L means the 456th amino acid in the spike protein changed from phenylalanine (F) to leucine (L). ORF1a:A690V means that the 690th amino acid in the protein encoded by open reading frame 1a changed from alanine (A) to valine (V).

Here's a review of how PANGO labels and aliases, WHO designations, and nicknames work for variants.

whn.global/common-names-f…

When you hear about "convergence", that means that multiple lineages are independently ending up with the same mutations (mutations occur by chance but if they increase reproductive success, e.g. by conferring immune escape, they will become more common over generations).

Here is the latest summary of convergent mutations in the spike protein across XBB lineages, by @dfocosi.

As you can see, *many* lineages have ended up with S486X and many (including Eris EG.5.1) have F456L (see above).

Understanding the different mutations is also useful for knowing whether new boosters or recent past infection will provide protection (from severe acute illness) against newer variants.

For example, updated boosters will target Kraken (XBB.1.5), but Kraken is on the way out.

Will boosters aimed at Kraken (XBB.1.5) work against Eris (EG.5.1 = XBB.1.9.2.5.1)?

Well, their spike proteins differ by only two mutations: S:F456L and S:Q52H. Overall, the boosters should still match quite well.

https://twitter.com/LongDesertTrain/status/1687484931067248640?t=8KGXHrG8GmWOezEjK0ctkg&s=19

But mutations like S:F456L are certainly not irrelevant in this context.

https://twitter.com/yunlong_cao/status/1687879512237993986?t=G14dJaOhifglRbQBzR-Qaw&s=19