Thread by @firefoxx66

Two new variants are now up on the #SARSCoV2 #COVID19 Mutations of Interest site! 🎉

Added
- Spike 69 deletion (S:H69-)
- Spike V1122L (S:V1122L) - primarily circulating in Sweden.

(More detail on each on the site coming soon - but thread below!)

1/9

github.com/emmahodcroft/c…

S:H69- is of particular interest, as it's part of a double-deletion (also position 70) that's appeared at least 3 times independently in conjunction with receptor binding domain (RBD) mutations: N501Y, N439K, & Y453F.

2/9

nextstrain.org/groups/neherla…

Below, the yellow is N439K, the orange is Y453F associated with Denmark (we see Y453F mutation multiple times) & the red is N501Y (again, we see N501Y mutation multiple times). Each of these RBD mutations also exists without the 69/70 deletion.

3/9

nextstrain.org/groups/neherla…

Scientists are interested in RBD mutations because they can play a role in immunity (they 'stick out') & cell binding (infecting cells).

Here's positions of 439, 453, & 501 on spike. 3 copies make up each spike & here, 1 is shown open & binding to the cell receptor (green)

3/9

A recent preprint by @GuptaR_lab gives a great summary of the 3 times 69/70del has appeared (& highlights the the recent 'new UK variant' which has 501Y+69/70del).

They note the deletion may impact and/or be in response to immunity.

4/9

biorxiv.org/content/10.110…

They predict that the 60/70del 'tucks in' a loop on the side of spike (left pic, going from blue to green - right pic, shows position of 69/70 on a zoomed-out spike).

This 'tuck in' may mean the virus can avoid antibodies that would bind to that area.

5/9

Importantly the "real life" implications of this deletion are unknown. Scientists are looking at this now - we should be patient to hear more information.

Vaccines cause you to make antibodies to MANY parts of spike - something like is not expected to mean they don't work.

6/9

S:V1122L is less common - we see it only in about 100 sequences. It is positioned at the very bottom of spike, near where it attaches to the membrane of the virus (which spike 'sticks out' of). This may or may not have any functional significance.

7/9

A zoomed-in view of the cluster with S:V1122L shows it's primarily in Sweden, though also found in Norway, UK, Denmark, and Latvia.

As I said, it's a small cluster & not much known about it - but we'll keep monitoring it!

8/9

nextstrain.org/groups/neherla…

I'm now tracking 10 #SARSCoV2 'Mutations of Interest' on this page - you can see all the 'focal' @nextstrain builds & information about each (still under construction!) here:

If you have more information on any of the mutations, please let me know!

9/9

github.com/emmahodcroft/c…